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Efficacy and Safety Study of Certolizumab Pegol (CZP) Versus Active Comparator and Placebo in Subjects With Plaque Psoriasis (PSO) (CIMPACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02346240
Recruitment Status : Completed
First Posted : January 26, 2015
Results First Posted : July 18, 2018
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Psoriasis
Plaque Psoriasis
Interventions Biological: Certolizumab Pegol
Biological: Etanercept
Other: Placebo
Enrollment 559
Recruitment Details This ongoing study started to enroll participants in February 2015, from multiple sites in Europe and United States. 559 participants are included in the Randomized Set (RS) shown in the Participant Flow.
Pre-assignment Details Provided data are Interim Results up to Week 48.
Arm/Group Title Placebo Q2W Etanercept CZP 200 mg Q2W CZP 400 mg Q2W Placebo/Placebo Q2W Etanercept/Placebo Q2W Etanercept/CZP 200 mg Q2W CZP 200 mg Q2W/Placebo Q2W CZP 200 mg Q2W/CZP 200 mg Q2W CZP 200 mg Q2W/CZP 400 mg Q4W CZP 400 mg Q2W/Placebo Q2W CZP 400 mg Q2W/CZP 200 mg Q2W CZP 400 mg Q2W/CZP 400 mg Q2W Placebo Q2W/Escape CZP 400 mg Q2W Etanercept/Escape CZP 400 mg Q2W CZP 200 mg Q2W/Escape CZP 400 mg Q2W CZP 400 mg Q2W/Escape CZP 400 mg Q2W
Hide Arm/Group Description

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.

-PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) Or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

This arm consisted of subjects initially randomized in the Placebo arm, who achieved a PASI75 response at Week 16 and continued to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q4W in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q2W in the Maintenance Period (Week 16 to Week 48). This arm consisted of subjects initially randomized in the Placebo arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Subjects who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study. This arm consisted of subjects initially randomized in the Etanercept arm, who did not achieve a PASI75 response at Week 16 escaped from the treatment and received CZP 400 mg every two weeks. Subjects who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study. This arm consisted of subjects initially randomized in the CZP 200 mg arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Subjects who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study. This arm consisted of subjects initially randomized in the CZP 400 mg arm, who did not achieve a PASI75 response at Week 16 escaped from the blinded treatment and received CZP 400 mg every two weeks. Subjects who did not achieve PASI50 after 16 weeks of unblinded treatment were withdrawn from the study.
Period Title: Initial Period (Baseline to Week 16)
Started 57 170 165 167 0 0 0 0 0 0 0 0 0 0 0 0 0
Completed Week 16 55 159 159 162 0 0 0 0 0 0 0 0 0 0 0 0 0
Finished Wk16 Started Maintenance Period 55 159 159 160 0 0 0 0 0 0 0 0 0 0 0 0 0
Completed 55 159 159 160 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 2 11 6 7 0 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             4             1             1             0             0             0             0             0             0             0             0             0             0             0             0             0
Lack of Efficacy             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0
Protocol Violation             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0
Lost to Follow-up             1             2             1             3             0             0             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             1             2             3             2             0             0             0             0             0             0             0             0             0             0             0             0             0
Non-compliance             0             1             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0
Subject missed 3 visits             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0             0
Period Title: Finished Wk16 Entered Maintenance Period
Started 0 0 0 0 2 24 50 22 44 44 25 50 49 53 85 49 36
Completed 0 0 0 0 2 23 48 20 40 43 23 47 49 46 71 36 30
Not Completed 0 0 0 0 0 1 2 2 4 1 2 3 0 7 14 13 6
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             1             2             0             0             0             0             1             4             1             2
Lack of Efficacy             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             3             0
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0
Withdrawal by Subject             0             0             0             0             0             1             1             1             1             0             1             2             0             2             4             1             0
Did not achieve PASI50             0             0             0             0             0             0             0             0             0             0             0             0             0             3             3             8             4
Moved out of state             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0
Sponsor decision due to non-compliance             0             0             0             0             0             0             0             0             1             0             0             1             0             1             1             0             0
Adverse events and alcohol problem             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
Patient’s decisions             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0
Unavailability due to business trip             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0
Arm/Group Title Placebo Q2W Etanercept CZP 200 mg Q2W CZP 400 mg Q2W Total Title
Hide Arm/Group Description

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.

-PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) Or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

[Not Specified]
Overall Number of Baseline Participants 57 170 165 167 559
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Randomized Set consisting of all subjects randomized into the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 170 participants 165 participants 167 participants 559 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
53
  93.0%
157
  92.4%
153
  92.7%
156
  93.4%
519
  92.8%
>=65 years
4
   7.0%
13
   7.6%
12
   7.3%
11
   6.6%
40
   7.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 170 participants 165 participants 167 participants 559 participants
46.5  (12.5) 44.6  (14.1) 46.7  (13.5) 45.4  (12.4) 45.7  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 170 participants 165 participants 167 participants 559 participants
Female
23
  40.4%
43
  25.3%
52
  31.5%
60
  35.9%
178
  31.8%
Male
34
  59.6%
127
  74.7%
113
  68.5%
107
  64.1%
381
  68.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 170 participants 165 participants 167 participants 559 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   0.6%
3
   1.8%
3
   1.8%
7
   1.3%
Black or African American
0
   0.0%
3
   1.8%
2
   1.2%
2
   1.2%
7
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
57
 100.0%
163
  95.9%
158
  95.8%
162
  97.0%
540
  96.6%
Other/mixed
0
   0.0%
3
   1.8%
2
   1.2%
0
   0.0%
5
   0.9%
1.Primary Outcome
Title Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 12
Hide Description The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) Etanercept (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.

-PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 170 165 167
Measure Type: Number
Unit of Measure: percentage of participants
5.0 53.3 61.3 66.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 61.6
Confidence Interval (2-Sided) 95%
52.1 to 71.2
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 56.2
Confidence Interval (2-Sided) 95%
46.4 to 66.0
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO.
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 37.988
Confidence Interval (2-Sided) 95%
11.312 to 127.576
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO.
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 30.023
Confidence Interval (2-Sided) 95%
8.971 to 100.481
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
2.7 to 24.1
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Etanercept Q2W (RS).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
-2.9 to 18.9
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Etanercept Q2W (RS).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0152
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. ETN.
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.756
Confidence Interval (2-Sided) 95%
1.114 to 2.768
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Etanercept (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1523
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. ETN
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.388
Confidence Interval (2-Sided) 95%
0.886 to 2.175
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Subjects Who Achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 12
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) Etanercept (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.

-PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 170 165 167
Measure Type: Number
Unit of Measure: percentage of participants
1.9 39.2 39.8 50.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 48.5
Confidence Interval (2-Sided) 95%
39.33 to 57.63
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
28.88 to 46.96
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 56.129
Confidence Interval (2-Sided) 95%
7.787 to 404.555
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0004
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 36.566
Confidence Interval (2-Sided) 95%
5.061 to 264.196
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 12
Hide Description The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) Etanercept (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

Etanercept (ETN) 50 mg subcutaneous (sc) injections twice per week throughout Week 11.5.

-PASI75 responders at Week 16 were re-randomized to either CZP (loading dose of 400 mg at Weeks 16, 18, and 20 followed by 200 mg Q2W) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 170 165 167
Measure Type: Number
Unit of Measure: percentage of participants
0.2 27.1 31.2 34.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 33.8
Confidence Interval (2-Sided) 95%
20.68 to 46.98
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 31.0
Confidence Interval (2-Sided) 95%
18.18 to 43.80
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 39.949
Confidence Interval (2-Sided) 95%
8.407 to 189.828
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 35.084
Confidence Interval (2-Sided) 95%
7.363 to 167.179
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 16
Hide Description The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 165 167
Measure Type: Number
Unit of Measure: percentage of participants
3.8 68.2 74.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 70.9
Confidence Interval (2-Sided) 95%
62.15 to 79.59
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 64.4
Confidence Interval (2-Sided) 95%
55.12 to 73.63
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 76.277
Confidence Interval (2-Sided) 95%
17.952 to 324.094
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 55.413
Confidence Interval (2-Sided) 95%
13.135 to 233.782
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Subjects Who Achieve a Physician’s Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2 Category Improvement) at Week 16
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 165 167
Measure Type: Number
Unit of Measure: percentage of participants
3.4 48.3 58.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 55.0
Confidence Interval (2-Sided) 95%
45.59 to 64.35
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 44.9
Confidence Interval (2-Sided) 95%
35.39 to 54.49
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 40.717
Confidence Interval (2-Sided) 95%
9.741 to 170.198
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 27.165
Confidence Interval (2-Sided) 95%
6.504 to 113.453
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI90) Response at Week 16
Hide Description The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set (RS) consisted of all subjects randomized into the study. Missing data were handled using the Markov Chain Monte Carlo (MCMC) method for multiple imputation.
Arm/Group Title Placebo Q2W (RS) CZP 200 mg Q2W (RS) CZP 400 mg Q2W (RS)
Hide Arm/Group Description:

Placebo subcutaneous (sc) injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 continued to receive blinded Placebo. PASI75 non-responders at Week 16 were removed from blinded study medication and escaped to Certolizumab pegol (CZP) 400 mg Q2W. Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study.

Subjects could enter a 96-week open-label extension period after completing the Maintenance Period (Weeks 16-48) and receive CZP under certain conditions.

CZP 400 mg injections at Weeks 0, 2, 4, followed by CZP 200 mg every 2 weeks (Q2W) from Week 6 to Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to receive either CZP 200 mg Q2W or CZP 400 mg every 4 weeks (Q4W); with Placebo administered on alternate dosing weeks to maintain the blind) or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

CZP 400 mg injections every 2 weeks (Q2W) through Week 14. Treatment received from Week 16-48 is based on initial treatment and response to treatment:

-PASI75 responders at Week 16 were re-randomized to CZP 200 mg Q2W or CZP 400 mg Q2W or Placebo Q2W. Subjects who did not achieve a PASI75 response at Week 16 were removed from blinded study medication and escaped to CZP 400 mg Q2W.

Subjects who received unblinded CZP 400 mg Q2W for 16 weeks and did not achieve a PASI50 response were withdrawn from the study. Subjects could enter a 96-week open-label extension period after completing the Maintenance Period and receive CZP under certain conditions.

Overall Number of Participants Analyzed 57 165 167
Measure Type: Number
Unit of Measure: percentage of participants
0.3 39.8 49.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 48.8
Confidence Interval (2-Sided) 95%
34.22 to 63.41
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 400 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Estimated responder rate, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Estimated difference in responder rate
Estimated Value 39.5
Confidence Interval (2-Sided) 95%
25.58 to 53.38
Estimation Comments Estimate and 95 % CI for difference in proportion of responders for CZP 200 mg Q2W (RS) versus Placebo Q2W (RS).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 400 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 400 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 72.278
Confidence Interval (2-Sided) 95%
14.650 to 356.602
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo Q2W (RS), CZP 200 mg Q2W (RS)
Comments The statistical analysis of the co-primary efficacy variables and key secondary efficacy variables accounted for multiplicity by using a fixed sequence testing procedure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is evaluated at a 2-sided significance level for CZP 200 mg vs. PBO
Method Regression, Logistic
Comments Odds ratios, CIs, p-values based on a logistic regression model with factors for treatment, region, prior biologic exposure.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 49.527
Confidence Interval (2-Sided) 95%
10.002 to 245.256
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Proportion of Subjects Who Achieve a Psoriasis Activity and Severity Index (PASI75) Response at Week 48 for Those Achieving PASI75 at Week 16
Hide Description The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The Week 16 Randomized Set (WK16RS) consisted of all subjects who achieved a PASI75 response at Week 16 and were re-randomized into the double-blind, placebo-controlled Maintenance Treatment Period.
Arm/Group Title Placebo/Placebo Q2W (RS) Etanercept/Placebo Q2W (RS) Etanercept/CZP 200 mg Q2W (RS) CZP 200 mg Q2W/Placebo Q2W (RS) CZP 200 mg Q2W/CZP 200 mg Q2W (RS) CZP 200 mg Q2W/CZP 400 mg Q4W (RS) CZP 400 mg Q2W/Placebo Q2W (RS) CZP 400 mg Q2W/CZP 200 mg Q2W (RS) CZP 400 mg Q2W/CZP 400 mg Q2W (RS)
Hide Arm/Group Description:
This arm consisted of subjects initially randomized in the Placebo arm, who achieved a PASI75 response at Week 16 and continued to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the Etanercept arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 200 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q4W in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded Placebo in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 200 mg Q2W in the Maintenance Period (Week 16 to Week 48).
This arm consisted of subjects initially randomized in the CZP 400 mg arm, who achieved a PASI75 response at Week 16 and were re-randomized to receive blinded CZP 400 mg Q2W in the Maintenance Period (Week 16 to Week 48).
Overall Number of Participants Analyzed 2 24 50 22 44 44 25 50 49
Measure Type: Number
Unit of Measure: percentage of participants
100 8.3 82.0 45.5 79.5 88.6 36.0 80.0 98.0
Time Frame Adverse Events (AEs) were collected from Baseline (Week 0) until Week 48.
Adverse Event Reporting Description Per study design, most of the subjects randomized to PBO at Week 0 escaped to CZP 400mg Q2W at Week 16. All subjects randomized to ETN at Week 0 switched to PBO or CZP at Week 16. Thus, the PBO and ETN arms had lower exposure compared to the CZP arms. The exposure imbalance across treatment arms could lead to misinterpretation & questionable conclusions comparing simple counts & percentages of AEs. Thus, AEs reported while subjects were on PBO or ETN treatment are not included in this summary.
 
Arm/Group Title CZP 200 mg Q2W (TCS) CZP 400 mg Q2W (TCS)
Hide Arm/Group Description This arm consisted of all subjects who received CZP 200 mg at any time during the study. This arm consisted of all subjects who received CZP 400 mg at any time during the study.
All-Cause Mortality
CZP 200 mg Q2W (TCS) CZP 400 mg Q2W (TCS)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/265 (0.00%)      0/354 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
CZP 200 mg Q2W (TCS) CZP 400 mg Q2W (TCS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/265 (4.53%)      23/354 (6.50%)    
Cardiac disorders     
Cardiac failure * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Acute coronary syndrome * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Eye disorders     
Cataract * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Gastrointestinal disorders     
Abdominal pain * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Haemorrhoids * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Peptic ulcer * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Hepatitis * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Infections and infestations     
Gastroenteritis * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Pancreas infection * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Escherichia sepsis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Endophthalmitis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Pneumonia * 1  1/265 (0.38%)  1 1/354 (0.28%)  1
Sepsis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Erysipelas * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Tuberculosis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Pyelonephritis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Injury, poisoning and procedural complications     
Concussion * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Foot fracture * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Forearm fracture * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Lower limb fracture * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Ulna fracture * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Wrist fracture * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Laceration * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Facial bones fracture * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Rib fracture * 1  1/265 (0.38%)  1 1/354 (0.28%)  1
Musculoskeletal and connective tissue disorders     
Polymyalgia rheumatica * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Compartment syndrome * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Osteoarthritis * 1  1/265 (0.38%)  1 1/354 (0.28%)  1
Psoriatic arthropathy * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anaplastic oligodendroglioma * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Nervous system disorders     
Migraine * 1  0/265 (0.00%)  0 2/354 (0.56%)  2
Primary progressive multiple sclerosis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Pregnancy, puerperium and perinatal conditions     
Pregnancy with contraceptive device * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Psychiatric disorders     
Bipolar I disorder * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Renal and urinary disorders     
Nephrolithiasis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
Reproductive system and breast disorders     
Uterine cyst * 1  1/265 (0.38%)  1 0/354 (0.00%)  0
Skin and subcutaneous tissue disorders     
Guttate psoriasis * 1  0/265 (0.00%)  0 1/354 (0.28%)  1
1
Term from vocabulary, MedDRA18.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CZP 200 mg Q2W (TCS) CZP 400 mg Q2W (TCS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   69/265 (26.04%)      91/354 (25.71%)    
Infections and infestations     
Nasopharyngitis * 1  35/265 (13.21%)  42 44/354 (12.43%)  49
Upper respiratory tract infection * 1  16/265 (6.04%)  21 29/354 (8.19%)  37
Viral upper respiratory tract infection * 1  14/265 (5.28%)  20 8/354 (2.26%)  9
Vascular disorders     
Hypertension * 1  10/265 (3.77%)  11 17/354 (4.80%)  17
1
Term from vocabulary, MedDRA18.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: +1844 599 ext 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
ClinicalTrials.gov Identifier: NCT02346240     History of Changes
Other Study ID Numbers: PS0003
2014-003492-36 ( EudraCT Number )
First Submitted: January 20, 2015
First Posted: January 26, 2015
Results First Submitted: June 22, 2018
Results First Posted: July 18, 2018
Last Update Posted: January 8, 2019