Three Dose Levels of CP-690,550 Monotherapy Versus Placebo, Administered Orally Twice Daily (BID) for 6 Weeks

Study Overview
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Brief Summary
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The study's objective is to compare the efficacy of 3 dose levels of oral CP-690,550 monotherapy (5 mg, 15 mg, and 30 mg twice daily [BID]) versus placebo administered over 6 weeks for the treatment of the signs and symptoms of subjects with active rheumatoid arthritis (RA).

Official Title
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A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Compare 3 Dose Levels Of CP-690,550 Versus Placebo, Administered Orally Twice Daily (BID) For 6 Weeks, In The Treatment Of The Signs And Symptoms Of Subjects With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* 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: The subject has a history of inadequate response to at least 1, but no more than 4, of the following DMARDs: sulfasalazine, injectable gold, methotrexate, leflunomide, cyclosporine, or a thiopurine derivative (azathioprine or 6-mercaptopurine) Exclusion Criteria: Current Therapy With Any DMARD Or Biologic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: 5 mg BID<br>CP 690,550 5 mg BID | Drug: CP-690,550<br>* Oral tablets administered at a dose of 5 mg BID for 6 weeks<br>|
| Experimental: 15 mg BID<br>CP 690,550 15 mg BID | Drug: CP-690,550<br>* Oral tablets administered at a dose of 15 mg BID for 6 weeks<br>|
| Experimental: 30 mg BID<br>Oral tablets administered at a dose of 30 mg BID for 6 weeks | Drug: CP-690,550<br>* 30 mg BID for 6 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo tablets<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 6 | 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). | Week 6 | 

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 1, 2, 4, and 8 | 
| 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 1, 2, 4, 6, and 8 | 
| 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 1, 2, 4, 6, and 8 | 
| Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve | ACR-n: calculated 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 AUC of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC. | Baseline up to Week 6 | 
| 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 1, 2, 4, 6, and 8 | 
| Change From Baseline in Tender Joints Count (TJC) at Week 1, 2, 4, 6 and 8 | 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 indicated an improvement. | Baseline, Week 1, 2, 4, 6, and 8 | 
| 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 1, 2, 4, 6, and 8 | 
| Change From Baseline in Swollen Joints Count (SJC) at Week 1, 2, 4, 6 and 8 | 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 1, 2, 4, 6, and 8 | 
| 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 millimeter (mm) Visual Analog Scale (VAS) where 0 mm = very well and 100 mm = very poorly. | Baseline, Week 1, 2, 4, 6, and 8 | 
| Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 1, 2, 4, 6 and 8 | 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 1, 2, 4, 6, and 8 | 
| 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 1, 2, 4, 6, and 8 | 
| Change From Baseline in Physician Global Assessment of Arthritis at Week 1, 2, 4, 6 and 8 | 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 1, 2, 4, 6, and 8 | 
| Patient Assessment of Arthritis Pain | 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 1, 2, 4, 6, and 8 | 
| Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 6 and 8 | 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 1, 2, 4, 6, and 8 | 
| 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 1, 2, 4, 6, and 8 | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 1, 2, 4, 6 and 8 | 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 1, 2, 4, 6, and 8 | 
| 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 liter (mg/L) to 100 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 1, 2, 4, 6, and 8 | 
| Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 6 and 8 | 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 mg/L to 100 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 1, 2, 4, 6, and 8 | 
| Disease Activity Score Using 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 ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and less than (<) 2.6 = remission. | Baseline, Week 1, 2, 4, 6, and 8 | 
| Change From Baseline in Disease Activity Score Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 1, 2, 4, 6, and 8 | DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and <2.6 = remission. | Baseline, Week 1, 2, 4, 6, and 8 | 
| Number of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP) | Disease improvement was classified as good, moderate, and no change 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 improvement. Scores of good and moderate were considered to have therapeutic response. | Baseline, Week 1, 2, 4, 6, and 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral JAK inhibitor, clinical trial, joint diseases, anti-Inflammatory agents, rheumatic diseases, DMARD, Antirheumatic Agents, Autoimmune Diseases, Immune System Diseases