Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors

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ClinicalTrials.gov Identifier: NCT00960440

Recruitment Status : Completed

First Posted : August 17, 2009

Results First Posted : January 10, 2013

Last Update Posted : December 19, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Pfizer

Study Description

Brief Summary:

This study will test if CP-690,550 is safe and effective in rheumatoid arthritis patients taking methotrexate who have an inadequate response to tumor necrosis factor inhibitor treatment.

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: CP-690,550 Drug: Placebo	Phase 3

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	399 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate With Inadequate Response To TNF Inhibitors
Study Start Date :	October 2009
Actual Primary Completion Date :	March 2011
Actual Study Completion Date :	March 2011

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Rheumatoid arthritis

MedlinePlus related topics: Arthritis Rheumatoid Arthritis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sequence 1	Drug: CP-690,550 Oral tablets administered at 5 mg BID daily for 6 months during the double-blind, placebo-controlled period.
Experimental: Sequence 2	Drug: CP-690,550 Oral tablets administered at 10 mg BID daily for 6 months during the double-blind, placebo-controlled period.
Placebo Comparator: Sequence 3	Drug: Placebo Oral placebo tablets administered BID daily during the first 3 months of the double-blind, study period. Other Name: double-blind, placebo-controlled phase Drug: CP-690,550 Oral tablets administered at 5 mg BID daily during the second 3 months of the double-blind, study period. Other Name: double-blind, extension phase
Placebo Comparator: Sequence 4	Drug: Placebo Oral placebo tablets administered BID daily during the first 3 months of the double-blind, placebo-controlled period. Other Name: double-blind, placebo-controlled phase Drug: CP-690,550 Oral tablets administered at 10 mg BID daily during the second 3 months of the double-blind, study period. Other Name: double-blind, extension phase

Outcome Measures

Primary Outcome Measures :

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 3 [ Time Frame: Month 3 ]
ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joints count (TJC); >= 20% improvement in swollen joints count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Month 3 [ Time Frame: Baseline, Month 3 ]
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities:dress/groom;arise;eat; walk;reach;grip; hygiene;common activities over past week. Each item scored on 4-point scale from 0-3:0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3:0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3 [ Time Frame: Month 3 ]
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR)(millimeter/hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (<=)3.2 implied low disease activity, greater than (>)3.2 to 5.1 implied moderate to high disease activity, less than (<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

Secondary Outcome Measures :

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 2 and Month 1 [ Time Frame: Week 2, Month 1 ]
ACR20 response: >=20% improvement in TJC; >=20% improvement in SJC; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
ACR20 response: >=20% improvement in TJC; >=20% improvement in SJC; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 2, Month 1 and 3 [ Time Frame: Week 2, Month 1, 3 ]
ACR50 response: >= 50% improvement in TJC or SJC and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 4.5 and 6 [ Time Frame: Month 4.5 and 6 ]
ACR50 response: >= 50% improvement in TJC or SJC and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 2, Month 1 and 3 [ Time Frame: Week 2, Month 1, 3 ]
ACR70 response: >=70% improvement in TJC or SJC and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
ACR70 response: >=70% improvement in TJC or SJC and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 6 [ Time Frame: Month 6 ]
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.
Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, Month 1 and 3 [ Time Frame: Week 2, Month 1, 3 ]
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3:0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3:0=least difficulty and 3=extreme difficulty.
Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3:0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3:0=least difficulty and 3=extreme difficulty.
Patient Assessment of Arthritis Pain at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.
Patient Assessment of Arthritis Pain at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
Patient Global Assessment (PtGA) of Arthritis Pain at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
Physician Global Assessment of Arthritis at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
Physician Global Assessment of Arthritis at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
36-Item Short-Form Health Survey (SF-36) at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
SF-36 is a standardized survey evaluating 8 domains (of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
36-Item Short-Form Health Survey (SF-36) at Month 6 [ Time Frame: Month 6 ]
SF-36 is a standardized survey evaluating 8 domains (of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1 and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales:sleep disturbance,snoring,awakened short of breath,sleep adequacy,somnolence (range:0-100);sleep quantity (range:0-24),optimal sleep(yes/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem.Except adequacy,optimal sleep and quantity,higher scores=more impairment.Scores transformed(actual raw score[RS] minus lowest possible score divided by possible RS range*100);total score range:0-100;higher score=more intensity of attribute.
Medical Outcomes Study Sleep Scale (MOS-SS) at Month 6 [ Time Frame: Month 6 ]
Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales:sleep disturbance,snoring,awakened short of breath,sleep adequacy,somnolence (range:0-100);sleep quantity (range:0-24),optimal sleep(yes/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem.Except adequacy,optimal sleep and quantity,higher scores=more impairment.Scores transformed(actual raw score[RS] minus lowest possible score divided by possible RS range*100);total score range:0-100;higher score=more intensity of attribute.
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1, and 3 [ Time Frame: Baseline, Week 2, Month 1, 3 ]
MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not optimal by choosing yes or no. Number of participants with optimal sleep is reported.
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Month 6 [ Time Frame: Month 6 ]
MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not optimal by choosing yes or no. Number of participants with optimal sleep is reported.
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
FACIT-Fatigue Scale (FS):13-item questionnaire, participant scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-FS for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Month 6 [ Time Frame: Month 6 ]
FACIT-FS:13-item questionnaire, participant scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-FS for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.
Euro Quality of Life - 5 Dimensions (EQ-5D)- Health State Profile Utility Score at Baseline, Month 1 and 3 [ Time Frame: Baseline, Month 1, 3 ]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Euro Quality of Life - 5 Dimensions (EQ-5D) - Health State Profile Utility Score at Month 6 [ Time Frame: Month 6 ]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline, Month 3 [ Time Frame: Baseline, Month 3 ]
Rheumatoid Arthritis (RA)-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost:visit to doctor,non-medical practitioner,nursing home,hospital,surgery,emergency room(ER) treatment,diagnostic tests, over-night stay,home healthcare services, aids/devices used. Indirect costs associated with functional disability:employment status,willingness to work,work disability due to RA,sick leave,part time work,ability to perform chores,chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale;higher score=higher medical cost.
Work Productivity and Healthcare Resource Utilization (HCRU) at Month 6 [ Time Frame: Month 6 ]
RA-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, non-medical practitioner, nursing home, hospital, surgery, emergency room(ER) treatment, diagnostic tests, over-night stay, home healthcare services, aids/devices used. Indirect costs associated with functional disability: employment status, willingness to work, work disability due to RA, sick leave, part time work, ability to perform chores, chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale; higher score=higher medical cost.
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported.
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 6 [ Time Frame: Month 6 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported.
Number of Days as Assessed Using RA-HCRU at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends were reported.
Number of Days as Assessed Using RA-HCRU at Month 6 [ Time Frame: Month 6 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends were reported.
Number of Hours Per Day as Assessed RA-HCRU at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, hours affected per day and average number of hours missed work per day were reported.
Number of Hours Per Day as Assessed RA-HCRU at Month 6 [ Time Frame: Month 6 ]
RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, hours affected per day and average number of hours missed work per day were reported.
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
Work performance of participants on number of days bothered was based on 10-point scale, where higher score indicated lower work performance.
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 6 [ Time Frame: Month 6 ]
Work performance of participants on number of days bothered was based on 10-point scale, where higher score indicated lower work performance.
Work Limitations Questionnaire (WLQ) Score at Baseline and Month 3 [ Time Frame: Baseline, Month 3 ]
WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (TMS)(5-items); Physical Demands scale (PDS) (6-item); Mental-Interpersonal Demands Scale (MIDS) (9-items); Output Demands Scale (ODS) (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index (WLI), which represented percentage of lost work over time period relative to a normative population, was derived (total score: 0 [no loss] to 100 [complete loss of work]).
Work Limitations Questionnaire (WLQ) Score at Month 6 [ Time Frame: Month 6 ]
WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (TMS)(5-items); Physical Demands scale (PDS) (6-item); Mental-Interpersonal Demands Scale (MIDS) (9-items); Output Demands Scale (ODS) (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index (WLI), which represented percentage of lost work over time period relative to a normative population, was derived (total score: 0 [no loss] to 100 [complete loss of work]).

Other Outcome Measures:

Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Week 2, Month 1 and 3 [ Time Frame: Week 2, Month 1, 3 ]
DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.
Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 4.5 and 6 [ Time Frame: Month 4.5, 6 ]
DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.
Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 3 [ Time Frame: Month 3 ]
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.
Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 6 [ Time Frame: Month 6 ]
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adults with moderate to severe rheumatoid arthritis on a stable dose of methotrexate who have inadequate response to Tumor Necrosis Factor (TNF) inhibitors.

Exclusion Criteria:

Pregnancy, severe acute or chronic medical conditions, including serious infections or clinically significant laboratory abnormalities.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00960440

Locations

Show 92 study locations

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United States, Alabama
Pfizer Investigational Site
Birmingham, Alabama, United States, 35294
United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90033
Pfizer Investigational Site
Los Angeles, California, United States, 90095
Pfizer Investigational Site
San Diego, California, United States, 92108
United States, Connecticut
Pfizer Investigational Site
Farmington, Connecticut, United States, 06030-5353
Pfizer Investigational Site
Trumbull, Connecticut, United States, 06611
United States, Florida
Pfizer Investigational Site
Aventura, Florida, United States, 33180
Pfizer Investigational Site
Tampa, Florida, United States, 33614
United States, Georgia
Pfizer Investigational Site
Atlanta, Georgia, United States, 30342
United States, Idaho
Pfizer Investigational Site
Boise, Idaho, United States, 83702
Pfizer Investigational Site
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Pfizer Investigational Site
Springfield, Illinois, United States, 62704
United States, Indiana
Pfizer Investigational Site
Indianapolis, Indiana, United States, 46227
United States, Louisiana
Pfizer Investigational Site
New Orleans, Louisiana, United States, 70115
United States, Maine
Pfizer Investigational Site
Portland, Maine, United States, 04102
United States, Maryland
Pfizer Investigational Site
Cumberland, Maryland, United States, 21502
United States, Massachusetts
Pfizer Investigational Site
Worcester, Massachusetts, United States, 01610
United States, Mississippi
Pfizer Investigational Site
Flowood, Mississippi, United States, 39232
Pfizer Investigational Site
Tupelo, Mississippi, United States, 38801
United States, New Hampshire
Pfizer Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Pfizer Investigational Site
Voorhees, New Jersey, United States, 08043
United States, North Carolina
Pfizer Investigational Site
Rocky Mount, North Carolina, United States, 27804
United States, Pennsylvania
Pfizer Investigational Site
Bethlehem, Pennsylvania, United States, 18015-1153
Pfizer Investigational Site
Willow Grove, Pennsylvania, United States, 19090
Pfizer Investigational Site
Wyomissing, Pennsylvania, United States, 19610
United States, Tennessee
Pfizer Investigational Site
Hixson, Tennessee, United States, 37343
Pfizer Investigational Site
Knoxville, Tennessee, United States, 37909
Pfizer Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75231
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Pfizer Investigational Site
Fort Worth, Texas, United States, 76107
Pfizer Investigational Site
Houston, Texas, United States, 77034
Pfizer Investigational Site
Lubbock, Texas, United States, 79424
United States, Washington
Pfizer Investigational Site
Vancouver, Washington, United States, 98664
Pfizer Investigational Site
Vancouver, Washington, United States, 98684
Pfizer Investigational Site
Vancouver, Washington, United States, 98686
Australia, New South Wales
Pfizer Investigational Site
Kogarah, New South Wales, Australia, 2217
Australia, South Australia
Pfizer Investigational Site
Daw Park, South Australia, Australia, 5041
Australia, Victoria
Pfizer Investigational Site
Heidelberg, Victoria, Australia, 3081
Austria
Pfizer Investigational Site
Wien, Austria, 1090
Pfizer Investigational Site
Wien, Austria, 1100
Pfizer Investigational Site
Wien, Austria, A-1100
Pfizer Investigational Site
Wien, Austria
Belgium
Pfizer Investigational Site
Genk, Belgium, 3600
Pfizer Investigational Site
Hasselt, Belgium, 3500
Pfizer Investigational Site
Kortrijk, Belgium
Pfizer Investigational Site
Liège, Belgium, 4020
Brazil
Pfizer Investigational Site
Goiania, GO, Brazil, 74110-120
Pfizer Investigational Site
Curitiba, PR, Brazil, 80060-240
Pfizer Investigational Site
Porto Alegre, RS, Brazil, 90610-000
Pfizer Investigational Site
Sao Paulo, SP, Brazil, 04266-010
Canada, Manitoba
Pfizer Investigational Site
Winnipeg, Manitoba, Canada, R3A 1M3
Canada, Ontario
Pfizer Investigational Site
Hamilton, Ontario, Canada, L8N 1Y2
Pfizer Investigational Site
Hamilton, Ontario, Canada, L8N 2B6
Pfizer Investigational Site
Ottawa, Ontario, Canada, K1H 1A2
Canada, Quebec
Pfizer Investigational Site
Montreal, Quebec, Canada, H2L 1S6
Pfizer Investigational Site
Pointe Claire, Quebec, Canada, H9R 3J1
France
Pfizer Investigational Site
Amiens, France, 80054
Pfizer Investigational Site
Lyon, France
Pfizer Investigational Site
Orleans Cedex 1, France, 45032
Pfizer Investigational Site
Orleans, France, 45000
Pfizer Investigational Site
Paris, France, 75014
Pfizer Investigational Site
Paris, France
Germany
Pfizer Investigational Site
Berlin, Germany, 10117
Pfizer Investigational Site
Berlin, Germany, 14163
Pfizer Investigational Site
Erlangen, Germany, 91054
Pfizer Investigational Site
Frankfurt am Main, Germany, 60590
Pfizer Investigational Site
Halle, Germany, 06108
Pfizer Investigational Site
Hamburg, Germany, 22081
Pfizer Investigational Site
Koeln, Germany, 50937
Pfizer Investigational Site
Leipzig, Germany, 04103
Pfizer Investigational Site
Rheine, Germany, 48431
Pfizer Investigational Site
Wuerzburg, Germany, 97080
Ireland
Pfizer Investigational Site
Croom, Co. Limerick, Ireland
Pfizer Investigational Site
Dublin, Ireland, 4
Italy
Pfizer Investigational Site
Firenze, Italy, 50139
Pfizer Investigational Site
Jesi, Italy
Korea, Republic of
Pfizer Investigational Site
Busan, Korea, Republic of, 602-715
Pfizer Investigational Site
Daegu, Korea, Republic of, 705-718
Pfizer Investigational Site
Seoul, Korea, Republic of, 135-720
Puerto Rico
Pfizer Investigational Site
San Juan, Puerto Rico, 00910
Spain
Pfizer Investigational Site
Santiago de Compostela, A Coruña, Spain, 15705
Pfizer Investigational Site
Merida, Badajoz, Spain, 06800
Pfizer Investigational Site
Bilbao, Bizkaia, Spain, 48013
Pfizer Investigational Site
Santander, Cantabria, Spain, 39008
Pfizer Investigational Site
Baracaldo, Vizcaya, Spain, 48903
Pfizer Investigational Site
Madrid, Spain, 28007
Pfizer Investigational Site
Valencia, Spain, 46017
Taiwan
Pfizer Investigational Site
Niao Sung Hsiang, Kaohsiung County, Taiwan, 833
Pfizer Investigational Site
Kweishan, Taoyuan County, Taiwan, 333
Pfizer Investigational Site
Changhua, Taiwan, 500
Pfizer Investigational Site
Kaohsiung, Taiwan, 813

Sponsors and Collaborators

Pfizer

Investigators

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Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dikranian AH, Gonzalez-Gay MA, Wellborne F, Alvaro-Gracia JM, Takiya L, Stockert L, Paulissen J, Shi H, Tatulych S, Curtis JR. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: an analysis of pooled data from phase 3 studies. RMD Open. 2022 May;8(1):e002103. doi: 10.1136/rmdopen-2021-002103.

Dikranian A, Gold D, Bessette L, Nash P, Azevedo VF, Wang L, Woolcott J, Shapiro AB, Szumski A, Fleishaker D, Wollenhaupt J. Frequency and Duration of Early Non-serious Adverse Events in Patients with Rheumatoid Arthritis and Psoriatic Arthritis Treated with Tofacitinib. Rheumatol Ther. 2022 Apr;9(2):411-433. doi: 10.1007/s40744-021-00405-w. Epub 2021 Dec 17.

Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.

Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.

Strand V, Kaine J, Alten R, Wallenstein G, Diehl A, Shi H, Germino R, Murray CW. Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib. Arthritis Res Ther. 2020 Oct 15;22(1):243. doi: 10.1186/s13075-020-02324-7.

Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:

Kivitz AJ, Cohen S, Keystone E, van Vollenhoven RF, Haraoui B, Kaine J, Fan H, Connell CA, Bananis E, Takiya L, Fleischmann R. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006. Epub 2018 Jul 19.

Hall S, Nash P, Rischmueller M, Bossingham D, Bird P, Cook N, Witcombe D, Soma K, Kwok K, Thirunavukkarasu K. Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population. Rheumatol Ther. 2018 Dec;5(2):383-401. doi: 10.1007/s40744-018-0118-2. Epub 2018 Jun 11.

Mariette X, Chen C, Biswas P, Kwok K, Boy MG. Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421. Epub 2018 Apr 2.

Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.

Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.

Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum In: Ann Rheum Dis. 2017 Mar;76(3):611.

Strand V, Burmester GR, Zerbini CA, Mebus CA, Zwillich SH, Gruben D, Wallenstein GV. Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial. Arthritis Care Res (Hoboken). 2015 Apr;67(4):475-83. doi: 10.1002/acr.22453.

Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.

Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, Koncz T, Soma K, Bradley J, Mebus C; ORAL Step investigators. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013 Feb 9;381(9865):451-60. doi: 10.1016/S0140-6736(12)61424-X. Epub 2013 Jan 5.

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Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00960440
Other Study ID Numbers:	A3921032
First Posted:	August 17, 2009 Key Record Dates
Results First Posted:	January 10, 2013
Last Update Posted:	December 19, 2018
Last Verified:	November 2018

Keywords provided by Pfizer:


randomized double-blind placebo-controlled investigational drug oral therapy safety and efficacy

Additional relevant MeSH terms:

Layout table for MeSH terms

Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases	Autoimmune Diseases Immune System Diseases Tofacitinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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