A Phase 2 Study For Patients With A Physician's Diagnosis 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 5 doses of CP-690,550 for the treatment of adults with active rheumatoid arthritis. Five out of seven subjects will receive CP-690,550. One out of seven will receive adalimumab (Humira®) and one out of seven will only receive inactive substances (placebo.)

Official Title
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A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Adalimumab
* Drug: CP-690-550
* Drug: CP-690-550
* Drug: CP-690-550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have active rheumatoid arthritis Subjects must have failed at least 1 disease modifying anti-rheumatic drug (DMARD) Subjects must not be currently taking any DMARD other than an antimalarial Exclusion Criteria: Subjects who discontinued any previous TNF inhibitor therapy for either lack of benefit or safety. Subjects who previously received adalimumab (Humira®) therapy for any reason. Subjects with evidence of blood disorders, chronic infections or untreated tuberculosis

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 |
| --- | --- |
| Active Comparator: 1<br> | Drug: Adalimumab<br>* 40mg subcutaneous injections every other week for 6 injections during week 0-10 with oral placebo BID. Subjects switched to CP-690,550 at week 12.<br>|
| Experimental: 2<br> | Drug: CP-690-550<br>* 15 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)<br>|
| Experimental: 3<br> | Drug: CP-690-550<br>* 10 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)<br>|
| Experimental: 4<br> | Drug: CP-690-550<br>* 5 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)<br>|
| Experimental: 5<br> | Drug: CP-690,550<br>* 3 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)<br>|
| Experimental: 6<br> | Drug: CP-690,550<br>* 1 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)<br>|
| Placebo Comparator: 7<br> | Drug: Placebo<br>* Placebo by mouth plus 6 placebo subcutaneous injections (week 0-10)<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: greater than or equal to (>=) 20 % improvement in tender joint count (TJC); >= 20% improvement in swollen joint 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, 10, 16, 20 and 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, 10, 12, 16, 20 and 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, 10, 12, 16, 20 and 24/ET | 
| Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) Response | ACR90 response: >= 90% improvement in TJC or SJC and 90% 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, 10, 12, 16, 20 and 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. 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, 10, 12 | 
| Tender Joint 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, 10, 12, 16, 20 and 24/ET | 
| Change From Baseline in Tender Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 or 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 indicated an improvement. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET | 
| Swollen Joint Counts (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, 10, 12, 16, 20 and 24/ET | 
| Change From Baseline in Swollen Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 | 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 indicated an improvement. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 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, 10, 12, 16, 20, 24/ET | 
| Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET | 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, 10, 12, 16, 20 and 24/ET | 
| Patient Global Assessment (PtGA) of Arthritis Pain | 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, 2, 4, 6, 8, 10, 12, 16, 20, 24/ET | 
| Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 10, 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, 10, 12, 16, 20, 24/ET | 
| Physician Global Assessment (PGA) 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, 10, 12, 16, 20, 24/ET | 
| Change From Baseline in Physician's Global Assessment (PGA) of Arthritis Pain at Week 2, 4, 6, 8, 10, 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, 10, 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 liter (mg/L) to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET | 
| Change From Baseline in C-reactive Protein (CRP) at Week 2, 4, 6, 8, 10, 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 ultrasensitive assay. Normal range of CRP is 0 mg/L to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 4, 6, 8, 10, 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, 10, 12, 16, 20, 24/ET | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 10, 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. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. | Baseline, Week 2, 4, 6, 8, 10, 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 greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and less than (<) 2.6 = remission. | Baseline, Week 2, 4, 6, 8, 10, 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, 10, 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 < 2.6 = remission. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET | 
| Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) | DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET | 
| Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET | DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR [mm/hour] and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission. | Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET | 
| Percentage of Participants With Disease Improvement Based on DAS28-4 (ESR) | Disease improvement was classified as good, moderate, and none based on improvement in DAS28-4 (ESR) from baseline and present DAS28-4 (ESR) 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, 10, 12, 16, 20, 24/ET | 
| Percentage of Participants With Disease Remission Based on Normal C-reactive Protein (CRP) | CRP value less than or equal to upper limit of normal (ULN) implied disease remission (ULN=4.9 mg/L). | Week 2, 4, 6, 8, 10, 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, 10, 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 Dimension (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 Dimension (EQ-5D)- Health State Profile Utility Score 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Janus Kinase 3 Clinical Trial