Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness and safety, over 6 months, of 6 dose regimens of CP-690,550, combined with methotrexate, for the treatment of adults with active rheumatoid arthritis.

Official Title
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A Phase 2B, Randomized, Double Blind, Placebo-Controlled, Multicenter Study To Compare 6 Dose Regimens Of CP-690,550 Vs. Placebo, Each Combined With Methotrexate, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate Alone

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active rheumatoid arthritis Inadequate response to stably dosed methotrexate Exclusion Criteria: Current therapy with any DMARD or biologic other than methotrexate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CP 690,550 1 mg BID<br> | Drug: CP-690,550<br>* 4 blinded tablets administered BID<br>|
| Experimental: CP 690,550 10 mg BID<br> | Drug: CP-690,550<br>* 4 blinded tablets administered BID<br>|
| Experimental: CP 690,550 15 mg<br> | Drug: CP-690,550<br>* 4 blinded tablets administered BID<br>|
| Experimental: CP 690,550 3 mg BID<br> | Drug: CP-690,550<br>* 4 blinded tablets administered BID<br>|
| Experimental: CP 690,550 5 mg BID<br> | Drug: CP-690,550<br>* 4 blinded tablets administered BID<br>|
| Experimental: CP-690,550 20 mg QD<br> | Drug: CP-690,550<br>* Oral tablets<br>|
| Placebo Comparator: Placebo<br>Dummy tablets | Other: placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | ACR20 response: >= 20% 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). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | 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. | Week 2, 4, 6, 8, 16, 20, 24/Early Termination (ET) | 
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | 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. | Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | 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. | Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve | ACR-n: calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. The area under the curve (AUC) for ACR-n is the measure of the area under the curve of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC. | Baseline up to Week 2, 4, 6, 8, 12 | 
| Tender Joints Count (TJC) | Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Tender Joints Count (TJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from baseline indicates an improvement. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Swollen Joints Count (SJC) | Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Swollen Joints Count (SJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from baseline indicates an improvement. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Patient Assessment of Arthritis Pain | 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. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | 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. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Patient Global Assessment (PtGA) of Arthritis | 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. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | 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. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Physician Global Assessment of Arthritis | Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Physician Global Assessment of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) | 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; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | 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; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Change = scores at observation minus score at Baseline, and total possible score ranged from -3 to 3. A negative value in change from baseline indicates an improvement. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| C-Reactive Protein (CRP) | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 milligram per deciliter (mg/dL) to 10 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in C-Reactive Protein (CRP) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra-sensitive assay. Normal range of CRP is 0 mg/dL to 10 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) | 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) less than or equal to (<=) 3.2 implied low disease activity and more than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<) 2.6 = remission. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | 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. | Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Percentage of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP) | Disease improvement was classified as good, moderate, and none based on improvement in DAS 28-3 (CRP) from baseline and present DAS 28-3 (CRP) score. Good: an improvement from baseline of >1.2 and a present score of <=3.2; none: an improvement of <=0.6 or >0.6 to <=1.2 with a present score of >5.1; remaining participants were classified as having moderate (Mod) improvement. Scores of good and moderate were considered to have therapeutic response. | Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| Percentage of Participants With Disease Remission Based on DAS28-3 (CRP) | DAS28-3 (CRP) defined remission was classified as a score of <2.6. | Week 2, 4, 6, 8, 12, 16, 20, 24/ET | 
| 36-Item Short-Form Health Survey (SF-36) | SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Baseline, Week 12, 24/ET | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET | SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Baseline, Week 12, 24/ET | 
| Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility Score | 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. | Baseline, Week 12, 24/ET | 
| Change From Baseline in Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility at Week 12 and 24/ET | 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. | Baseline, Week 12, 24/ET | 
| Medical Outcome Study- Sleep Scale (MOS-SS) | Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0)and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute. | Baseline, Week 2, 12, 24/ET | 
| Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET | Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range: 0-100); sleep quantity (Qua) (range: 0-24), and optimal (Opt) sleep (yes: 1, no: 0) and 9 item index measures of sleep disturbance were constructed to provide 2 composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range*100); total score range: 0 to 100; higher score = greater intensity of attribute. | Baseline, Week 2, 12, 24/ET | 
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | FACIT-Fatigue scale (FS) is a 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 score 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. | Baseline, Week 2, 12, 24/ET | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET | FACIT-FS is a 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 score 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. | Baseline, Week 2, 12, 24/ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMARD therapy