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Study to Investigate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years and Over With Moderate to Severe Atopic Dermatitis With the Option of Rescue Treatment in Flaring Subjects

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ClinicalTrials.gov Identifier: NCT03627767
Recruitment Status : Completed
First Posted : August 13, 2018
Results First Posted : September 20, 2021
Last Update Posted : September 20, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Dermatitis
Dermatitis, Atopic
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Interventions Drug: PF-04965842 100 mg
Drug: PF-04965842 200 mg
Drug: Placebo
Enrollment 1235
Recruitment Details Total 1235 participants were enrolled in 236 sites in 21 countries. Study started from 11 June 2018 and completed on 07 October 2020.
Pre-assignment Details Study Baseline: was defined as the last observation collected on or prior to Day 1 (first dose day) of study treatment. Randomization Baseline: was defined as the last observation collected between last dose of run-in treatment and Day 1 (first dose day) of randomized treatment. Rescue Baseline: was defined as the last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment.
Arm/Group Title PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
Hide Arm/Group Description Participants received 12 weeks induction treatment of 200 milligram (mg) oral tablets (each tablet of 100 mg) PF-04965842 once daily (QD) during an OL run-in period. Responders at the end of the 12-week OL run-in period entered the 40 week, double-blind (DB), maintenance treatment period. Responder criteria was defined as a) achieving an Investigator's Global Assessment (IGA) of clear (0) or almost clear (1) (on a 5-point scale), b) a reduction from IGA baseline of greater than or equal to (>= 2) points, and c) reaching an Eczema Area and Severity Index (EASI)-75 response compared to baseline score. Baseline score was the IGA score and EASI score obtained prior to dosing on Day 1. Non-responders had a choice to enroll into the PF-04965842 Long Term Extension (LTE) study B7451015 (NCT03422822) otherwise, they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
Period Title: Open-label (OL) Run-in Period (12 Weeks)
Started 1235 0 0 0 0
Treated 1233 0 0 0 0
Completed 798 0 0 0 0
Not Completed 437 0 0 0 0
Reason Not Completed
Adverse Event             48             0             0             0             0
Death             1             0             0             0             0
Lack of Efficacy             315             0             0             0             0
Lost to Follow-up             13             0             0             0             0
Protocol Violation             11             0             0             0             0
Withdrawal by Subject             40             0             0             0             0
Medication Error Without Associated Adverse Event             1             0             0             0             0
Withdrawal By Parent/Guardian             2             0             0             0             0
Other             4             0             0             0             0
Randomized but not treated             2             0             0             0             0
Period Title: Double-blind Treatment Period (40 Weeks)
Started 0 [1] 267 [2] 265 [2] 266 [2] 0
Participants Entered Rescue Period 0 208 109 44 0
Completed After Entering Rescue Period 0 201 99 41 0
Completed Without Entering Rescue Period 0 43 134 187 0
Completed 0 251 [3] 243 [4] 231 [5] 0
Not Completed 0 16 22 35 0
Reason Not Completed
Adverse Event             0             6             7             19             0
Lost to Follow-up             0             0             2             3             0
Protocol Violation             0             1             5             2             0
Withdrawal by Subject             0             9             6             10             0
Withdrawal By Parent/Guardian             0             0             1             0             0
Other             0             0             1             1             0
[1]
Participants did not enter into the DB period.
[2]
Participants who met the pre-defined criteria for DB.
[3]
208 entered RP+43 completed study in DB period
[4]
109 entered RP+134 completed study in DB period
[5]
44 entered RP+187 completed study in DB period
Period Title: Open-label Rescue Period (12 Weeks)
Started 0 0 [1] 0 [1] 0 [1] 361 [2]
Met Protocol-defined Flare Criteria 0 0 0 0 351
Completed 0 0 0 0 341
Not Completed 0 0 0 0 20
Reason Not Completed
Adverse Event             0             0             0             0             9
Lost to Follow-up             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             9
Other             0             0             0             0             1
[1]
Participants did not enter into the OL- Rescue Period.
[2]
Participants who met the pre-defined criteria for OL- Rescue Period.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB Total
Hide Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Total of all reporting groups
Overall Number of Baseline Participants 267 265 266 798
Hide Baseline Analysis Population Description
Full analysis set-randomized (FAS-RA) included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within Double-blind (DB) phase.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 265 participants 266 participants 798 participants
<18 years
49
  18.4%
49
  18.5%
47
  17.7%
145
  18.2%
Between 18 and 65 years
210
  78.7%
206
  77.7%
207
  77.8%
623
  78.1%
>=65 years
8
   3.0%
10
   3.8%
12
   4.5%
30
   3.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 265 participants 266 participants 798 participants
Female
126
  47.2%
117
  44.2%
116
  43.6%
359
  45.0%
Male
141
  52.8%
148
  55.8%
150
  56.4%
439
  55.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 265 participants 266 participants 798 participants
Hispanic or Latino
65
  24.3%
62
  23.4%
52
  19.5%
179
  22.4%
Not Hispanic or Latino
200
  74.9%
203
  76.6%
214
  80.5%
617
  77.3%
Unknown or Not Reported
2
   0.7%
0
   0.0%
0
   0.0%
2
   0.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 265 participants 266 participants 798 participants
American Indian or Alaska Native
4
   1.5%
2
   0.8%
1
   0.4%
7
   0.9%
Asian
38
  14.2%
41
  15.5%
45
  16.9%
124
  15.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
14
   5.2%
9
   3.4%
10
   3.8%
33
   4.1%
White
209
  78.3%
208
  78.5%
204
  76.7%
621
  77.8%
More than one race
2
   0.7%
3
   1.1%
5
   1.9%
10
   1.3%
Unknown or Not Reported
0
   0.0%
2
   0.8%
1
   0.4%
3
   0.4%
1.Primary Outcome
Title Percentage of Participants With Loss of Response: Double-blind (DB) Period
Hide Description Percentage of participants with loss of response requiring rescue treatment during double blind period was determined. Loss of response denoted as flare and was define as a loss of at least 50% of EASI total score at Week 12 and with an IGA score of 2 or higher. EASI quantifies severity of participant's atopic dermatitis (AD) based on both severity of lesion clinical signs and % of body surface area (BSA) affected. EASI is a composite scoring by AD clinical evaluator of degree of erythema, induration/papulation, excoriation, and lichenification for each of 4 body regions. EASI total score range from 0.0 to 72.0, with higher scores representing greater severity of AD. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores = more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate and 4 = severe.
Time Frame From Day 1 of up to Week 40 of double blind period
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set-randomized (FAS-RA) included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 265 266
Measure Type: Number
Unit of Measure: percentage of participants
77.5 39.6 16.5
2.Primary Outcome
Title Time to Loss of Response: Double-blind Period
Hide Description Time (in days) to loss of response based on achieving IGA >=2 was measured from date of first dose of randomized treatment until last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) and based on EASI, loss of at least 50% of EASI response at Week 12 and IGA score of 2 or higher. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores=more severity), reflecting global consideration of erythema, induration and scaling with scores 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. EASI composite score evaluates degree of erythema, induration/papulation, excoriation, and lichenification.
Time Frame From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window was extended +/- 45 Days due to COVID 19)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment. Here 'Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 207 105 44
Median (95% Confidence Interval)
Unit of Measure: days
28.0
(28.0 to 29.0)
323.0
(282.0 to 323.0)
NA [1] 
(NA to NA)
[1]
Median and 95% CI were not estimable as there were only few participant who had events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% confidence interval (CI).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate p-value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
0.211 to 0.341
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.070 to 0.136
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.255 to 0.516
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to First Loss of Response Based on Investigator's Global Assessment (IGA) Score of 2 or Higher: Double-blind Period
Hide Description Time (in days) to loss of response based on achieving IGA >=2 (for the first time) as measured from date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue). IGA assesses severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep, dark red lesions.
Time Frame From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window +/- 7 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least one dose of study medication within the double-blind phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment. Here, Overall 'Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 247 183 145
Median (95% Confidence Interval)
Unit of Measure: days
27.0
(26.0 to 28.0)
78.0
(32.0 to 112.0)
201.0
(177.0 to 282.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.286 to 0.424
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.176 to 0.270
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.503 to 0.780
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Weeks 12, 16, 28, 40, and 52: Double-blind Period
Hide Description IGA assessed severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep dark red lesions.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 264 266
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 266 participants 264 participants 265 participants
99.6
(98.9 to 100.0)
99.6
(98.9 to 100.0)
99.2
(98.2 to 100.0)
Week 16 Number Analyzed 267 participants 263 participants 266 participants
15.4
(11.0 to 19.7)
55.5
(49.5 to 61.5)
77.8
(72.8 to 82.8)
Week 28 Number Analyzed 267 participants 260 participants 262 participants
10.5
(6.8 to 14.2)
45.0
(39.0 to 51.0)
61.8
(55.9 to 67.7)
Week 40 Number Analyzed 265 participants 260 participants 259 participants
10.6
(6.9 to 14.3)
42.3
(36.3 to 48.3)
57.1
(51.1 to 63.2)
Week 52 Number Analyzed 264 participants 258 participants 257 participants
11.7
(7.9 to 15.6)
36.8
(30.9 to 42.7)
54.1
(48.0 to 60.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9495
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 1.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.5717
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.6 to 0.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.7 to 0.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 40.5
Confidence Interval (2-Sided) 95%
33.1 to 47.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 62.6
Confidence Interval (2-Sided) 95%
56.1 to 69.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 22.1
Confidence Interval (2-Sided) 95%
14.3 to 29.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 35.1
Confidence Interval (2-Sided) 95%
28.1 to 42.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 51.5
Confidence Interval (2-Sided) 95%
44.6 to 58.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.5
Confidence Interval (2-Sided) 95%
8.1 to 24.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 32.2
Confidence Interval (2-Sided) 95%
25.2 to 39.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 46.9
Confidence Interval (2-Sided) 95%
39.9 to 53.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 14.2
Confidence Interval (2-Sided) 95%
5.9 to 22.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.5
Confidence Interval (2-Sided) 95%
18.5 to 32.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 42.5
Confidence Interval (2-Sided) 95%
35.3 to 49.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
8.6 to 25.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=50% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema [E], induration/papulation [I], excoriation [Ex] and lichenification [L]) was scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin] and lower limbs [l] [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); where A = area score. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 264 266
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 266 participants 264 participants 265 participants
100.0
(98.6 to 100.0)
100.0
(98.6 to 100.0)
100.0
(98.6 to 100.0)
Week 16 Number Analyzed 267 participants 263 participants 266 participants
40.8
(34.9 to 46.7)
83.3
(78.8 to 87.8)
96.2
(94.0 to 98.5)
Week 28 Number Analyzed 267 participants 260 participants 262 participants
22.8
(17.8 to 27.9)
68.1
(62.4 to 73.7)
85.9
(81.7 to 90.1)
Week 40 Number Analyzed 265 participants 260 participants 259 participants
16.6
(12.1 to 21.1)
57.3
(51.3 to 63.3)
74.9
(69.6 to 80.2)
Week 52 Number Analyzed 264 participants 258 participants 257 participants
15.9
(11.5 to 20.3)
50.8
(44.7 to 56.9)
71.2
(65.7 to 76.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions. P-value was adjusted by disease severity at baseline and randomization strata.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 42.7
Confidence Interval (2-Sided) 95%
35.3 to 50.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 55.4
Confidence Interval (2-Sided) 95%
49.1 to 61.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
7.9 to 17.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 45.5
Confidence Interval (2-Sided) 95%
37.9 to 53.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 63.0
Confidence Interval (2-Sided) 95%
56.4 to 69.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 17.7
Confidence Interval (2-Sided) 95%
10.7 to 24.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 41.0
Confidence Interval (2-Sided) 95%
33.6 to 48.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 58.3
Confidence Interval (2-Sided) 95%
51.3 to 65.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 17.5
Confidence Interval (2-Sided) 95%
9.6 to 25.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 35.3
Confidence Interval (2-Sided) 95%
27.8 to 42.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 55.3
Confidence Interval (2-Sided) 95%
48.3 to 62.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 20.3
Confidence Interval (2-Sided) 95%
12.1 to 28.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 264 266
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 266 participants 264 participants 265 participants
99.2
(98.2 to 100.0)
100.0
(98.6 to 100.0)
99.6
(98.9 to 100.0)
Week 16 Number Analyzed 267 participants 263 participants 266 participants
27.0
(21.6 to 32.3)
76.0
(70.9 to 81.2)
92.5
(89.3 to 95.7)
Week 28 Number Analyzed 267 participants 260 participants 262 participants
18.0
(13.4 to 22.6)
60.4
(54.4 to 66.3)
80.5
(75.7 to 85.3)
Week 40 Number Analyzed 265 participants 260 participants 259 participants
15.1
(10.8 to 19.4)
54.2
(48.2 to 60.3)
71.8
(66.3 to 77.3)
Week 52 Number Analyzed 264 participants 258 participants 257 participants
14.0
(9.8 to 18.2)
46.5
(40.4 to 52.6)
65.8
(60.0 to 71.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.1848
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.3 to 1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.5971
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.9 to 1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 49.4
Confidence Interval (2-Sided) 95%
42.0 to 56.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 65.5
Confidence Interval (2-Sided) 95%
59.3 to 71.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
10.3 to 22.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 42.7
Confidence Interval (2-Sided) 95%
35.2 to 50.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 62.6
Confidence Interval (2-Sided) 95%
56.0 to 69.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 19.8
Confidence Interval (2-Sided) 95%
12.3 to 27.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 39.5
Confidence Interval (2-Sided) 95%
32.1 to 46.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 56.7
Confidence Interval (2-Sided) 95%
49.8 to 63.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 17.4
Confidence Interval (2-Sided) 95%
9.3 to 25.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 33.0
Confidence Interval (2-Sided) 95%
25.7 to 40.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 51.7
Confidence Interval (2-Sided) 95%
44.6 to 58.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 19.2
Confidence Interval (2-Sided) 95%
10.8 to 27.6
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=90% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 264 266
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 266 participants 264 participants 265 participants
84.6
(80.2 to 88.9)
87.1
(83.1 to 91.2)
86.4
(82.3 to 90.5)
Week 16 Number Analyzed 267 participants 263 participants 266 participants
13.9
(9.7 to 18.0)
51.3
(45.3 to 57.4)
77.1
(72.0 to 82.1)
Week 28 Number Analyzed 267 participants 260 participants 262 participants
10.5
(6.8 to 14.2)
46.9
(40.9 to 53.0)
64.5
(58.7 to 70.3)
Week 40 Number Analyzed 265 participants 260 participants 259 participants
12.1
(8.2 to 16.0)
41.5
(35.5 to 47.5)
58.7
(52.7 to 64.7)
Week 52 Number Analyzed 264 participants 258 participants 257 participants
10.6
(6.9 to 14.3)
37.6
(31.7 to 43.5)
54.5
(48.4 to 60.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3994
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-3.3 to 8.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.5542
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-4.1 to 7.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-6.5 to 5.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 37.5
Confidence Interval (2-Sided) 95%
30.2 to 44.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 63.3
Confidence Interval (2-Sided) 95%
56.8 to 69.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.5
Confidence Interval (2-Sided) 95%
17.7 to 33.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 36.9
Confidence Interval (2-Sided) 95%
29.9 to 44.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 54.2
Confidence Interval (2-Sided) 95%
47.3 to 61.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 17.2
Confidence Interval (2-Sided) 95%
8.9 to 25.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 29.8
Confidence Interval (2-Sided) 95%
22.7 to 37.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 46.7
Confidence Interval (2-Sided) 95%
39.6 to 53.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.9
Confidence Interval (2-Sided) 95%
8.5 to 25.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 27.4
Confidence Interval (2-Sided) 95%
20.4 to 34.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 43.8
Confidence Interval (2-Sided) 95%
36.7 to 50.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.8
Confidence Interval (2-Sided) 95%
8.4 to 25.2
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=100% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 267 264 266
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 266 participants 264 participants 265 participants
30.5
(24.9 to 36.0)
30.3
(24.8 to 35.8)
28.3
(22.9 to 33.7)
Week 16 Number Analyzed 267 participants 263 participants 266 participants
3.7
(1.5 to 6.0)
15.2
(10.9 to 19.5)
28.9
(23.5 to 34.4)
Week 28 Number Analyzed 267 participants 260 participants 262 participants
4.1
(1.7 to 6.5)
16.5
(12.0 to 21.1)
30.2
(24.6 to 35.7)
Week 40 Number Analyzed 265 participants 260 participants 259 participants
4.5
(2.0 to 7.0)
15.8
(11.3 to 20.2)
30.1
(24.5 to 35.7)
Week 52 Number Analyzed 264 participants 258 participants 257 participants
4.5
(2.0 to 7.1)
18.6
(13.9 to 23.4)
28.8
(23.3 to 34.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9313
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-7.5 to 8.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.6043
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-9.8 to 5.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-10.0 to 5.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
6.6 to 16.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.3
Confidence Interval (2-Sided) 95%
19.4 to 31.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 13.5
Confidence Interval (2-Sided) 95%
6.6 to 20.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
7.7 to 18.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 26.0
Confidence Interval (2-Sided) 95%
19.9 to 32.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
6.3 to 20.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
6.5 to 16.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.7
Confidence Interval (2-Sided) 95%
19.6 to 31.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 14.1
Confidence Interval (2-Sided) 95%
7.0 to 21.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 14.6
Confidence Interval (2-Sided) 95%
9.2 to 20.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 24.5
Confidence Interval (2-Sided) 95%
18.4 to 30.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
2.7 to 17.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Greater Than or Equal 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated worse disease status.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 258 254 250
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 12 Number Analyzed 230 participants 237 participants 232 participants
82.2
(77.2 to 87.1)
84.0
(79.3 to 88.6)
81.9
(76.9 to 86.9)
Week 16 Number Analyzed 252 participants 251 participants 250 participants
15.9
(11.4 to 20.4)
54.6
(48.4 to 60.7)
75.6
(70.3 to 80.9)
Week 28 Number Analyzed 258 participants 251 participants 245 participants
11.6
(7.7 to 15.5)
45.0
(38.9 to 51.2)
66.9
(61.0 to 72.8)
Week 40 Number Analyzed 257 participants 254 participants 246 participants
10.1
(6.4 to 13.8)
39.4
(33.4 to 45.4)
55.7
(49.5 to 61.9)
Week 52 Number Analyzed 252 participants 217 participants 204 participants
8.3
(4.9 to 11.7)
27.6
(21.7 to 33.6)
49.0
(42.2 to 55.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.6082
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-5.0 to 8.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9640
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-6.7 to 7.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-9.1 to 4.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 38.9
Confidence Interval (2-Sided) 95%
31.2 to 46.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 59.7
Confidence Interval (2-Sided) 95%
52.7 to 66.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 20.9
Confidence Interval (2-Sided) 95%
12.7 to 29.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 33.9
Confidence Interval (2-Sided) 95%
26.6 to 41.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 55.3
Confidence Interval (2-Sided) 95%
48.2 to 62.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 21.7
Confidence Interval (2-Sided) 95%
13.2 to 30.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 29.7
Confidence Interval (2-Sided) 95%
22.7 to 36.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 45.5
Confidence Interval (2-Sided) 95%
38.4 to 52.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.0
Confidence Interval (2-Sided) 95%
7.4 to 24.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 19.9
Confidence Interval (2-Sided) 95%
13.0 to 26.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was adjusted by disease severity at baseline and randomization strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 40.5
Confidence Interval (2-Sided) 95%
32.8 to 48.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 20.9
Confidence Interval (2-Sided) 95%
11.8 to 30.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in Body Surface Area (BSA) at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description 4 body regions evaluated: head and neck, upper limbs, trunk (including axillae, groin/genitals), lower limbs (including buttocks) excluding scalp, palms, soles. BSA calculated by handprint method. Number (No) of handprints (size of participant's hand with fingers in closed position) fitting in affected area of a body region was estimated. Maximum No of handprints were 10, 20, 30, 40 for head and neck, upper limbs, trunk, and lower limbs respectively. Surface area (SA) of body region equivalent to 1 handprint: 1 handprint=10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. %Change BSA for a body region was calculated as=total No of handprints in a body region* %SA equivalent to 1 handprint. %BSA for an individual: arithmetic mean of %BSA of all 4 body regions, ranged from 0-100%, higher values=greater AD severity.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 266 264 265
Median (Inter-Quartile Range)
Unit of Measure: percent change
Change at Week 12 Number Analyzed 266 participants 264 participants 265 participants
-95.6
(-100.0 to -88.5)
-96.7
(-100.0 to -91.5)
-96.7
(-100.0 to -89.2)
Change at Week 16 Number Analyzed 135 participants 223 participants 256 participants
-68.5
(-89.8 to -37.5)
-90.9
(-97.6 to -78.3)
-96.3
(-100.0 to -88.7)
Change at Week 28 Number Analyzed 64 participants 180 participants 227 participants
-85.2
(-95.8 to -63.5)
-93.8
(-99.5 to -81.4)
-96.4
(-100.0 to -85.7)
Change at Week 40 Number Analyzed 46 participants 151 participants 197 participants
-91.2
(-100.0 to -77.9)
-95.8
(-100.0 to -83.5)
-96.8
(-100.0 to -88.8)
Change at Week 52 Number Analyzed 42 participants 134 participants 185 participants
-91.5
(-100.0 to -77.9)
-96.9
(-100.0 to -83.4)
-96.9
(-100.0 to -88.2)
11.Secondary Outcome
Title Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3); severity scores added to give B (0-18). C: pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 265 264 265
Median (Inter-Quartile Range)
Unit of Measure: percent change
Change at Week 12 Number Analyzed 265 participants 264 participants 265 participants
-84.0
(-94.7 to -73.5)
-84.4
(-95.2 to -74.9)
-84.4
(-93.8 to -74.2)
Change at Week 16 Number Analyzed 134 participants 224 participants 256 participants
-50.4
(-68.3 to -32.1)
-71.7
(-87.8 to -60.5)
-83.6
(-95.1 to -70.6)
Change at Week 28 Number Analyzed 62 participants 177 participants 227 participants
-63.4
(-81.9 to -48.3)
-77.8
(-90.2 to -62.6)
-83.8
(-97.4 to -66.4)
Change at Week 40 Number Analyzed 46 participants 152 participants 196 participants
-74.4
(-89.5 to -60.6)
-77.1
(-94.1 to -64.3)
-84.6
(-98.6 to -68.4)
Change at Week 52 Number Analyzed 43 participants 132 participants 184 participants
-73.3
(-89.8 to -58.0)
-82.5
(-97.7 to -64.1)
-83.2
(-100.0 to -69.1)
12.Secondary Outcome
Title Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch and Sleep Loss at Weeks 12, 16, 28, 40 and 52: Double-blind Period
Hide Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region-head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
Time Frame Baseline, Weeks 12, 16, 28, 40 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
Hide Arm/Group Description:
Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
Overall Number of Participants Analyzed 264 264 261
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Pruritus VAS: Change at Week 12 Number Analyzed 264 participants 264 participants 261 participants
-6.1
(-6.3 to -5.9)
-6.1
(-6.3 to -5.9)
-6.1
(-6.3 to -5.9)
Pruritus VAS: Change at Week 16 Number Analyzed 264 participants 264 participants 261 participants
3.4
(3.0 to 3.7)
1.2
(1.0 to 1.5)
0.2
(-0.1 to 0.4)
Pruritus VAS: Change at Week 28 Number Analyzed 264 participants 264 participants 261 participants
2.4
(1.9 to 2.9)
1.1
(0.8 to 1.4)
0.5
(0.3 to 0.8)
Pruritus VAS: Change at Week 40 Number Analyzed 264 participants 264 participants 261 participants
2.2
(1.6 to 2.8)
1.2
(0.9 to 1.6)
0.4
(0.1 to 0.7)
Pruritus VAS: Change at Week 52 Number Analyzed 264 participants 264 participants 261 participants
1.8
(1.2 to 2.4)
1.3
(0.9 to 1.6)
0.5
(0.2 to 0.8)
Sleep Loss VAS: Change at Week 12 Number Analyzed 264 participants 264 participants 260 participants
-5.0
(-5.2 to -4.8)
-5.0
(-5.2 to -4.8)
-5.1
(-5.3 to -4.9)
Sleep Loss VAS: Change at Week 16 Number Analyzed 264 participants 264 participants 260 participants
2.3
(2.0 to 2.6)
0.5
(0.3 to 0.8)
0.0
(-0.2 to 0.2)
Sleep Loss VAS: Change at Week 28 Number Analyzed 264 participants 264 participants 260 participants
1.3
(0.9 to 1.7)
0.6
(0.4 to 0.9)
0.2
(0.0 to 0.4)
Sleep Loss VAS: Change at Week 40 Number Analyzed 264 participants 264 participants 260 participants
1.3
(0.8 to 1.8)
0.6
(0.3 to 0.9)
0.2
(0.0 to 0.4)
Sleep Loss VAS: Change at Week 52 Number Analyzed 264 participants 264 participants 260 participants
1.2
(0.7 to 1.8)
0.9
(0.5 to 1.2)
0.3
(0.0 to 0.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Pruritus VAS: Week 12: The least squares mean (LSM) differences between treatment groups were derived from the statistical model. Mixed model repeated measure (MMRM) contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9207
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Pruritus VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9998
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Pruritus VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-2.5 to -1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-3.6 to -2.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-1.4 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
Comments Pruritus VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.0 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
Comments Pruritus VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation