A Study to Assess the Effect of Tocilizumab on Signs and Symptoms in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This single arm, open label study will assess the safety and efficacy, with regard to reduction of signs and symptoms,of treatment with tocilizumab in patients with moderate to severe active rheumatoid arthritis. Patients will receive tocilizumab 8 mg/kg IV every 4 weeks for a total of 6 infusions. Patients already receiving methotrexate at entry into the study may continue with their treatment together with tocilizumab.The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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An Open Label Study to Evaluate the Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients,>=18 years of age; rheumatoid arthritis diagnosed >8 weeks and <4 years prior to baseline; naive to, or not responding well to, methotrexate; swollen joint count >=8 (66 joint count) and tender joint count>=8 (68 joint count) at screening and baseline. Exclusion Criteria: rheumatic autoimmune disease other than rheumatoid arthritis; patients with functional class IV rheumatoid arthritis; history of, or current, inflammatory joint disease other than rheumatoid arthritis, or other systemic autoimmune disorder.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8mg/kg iv every 4 weeks for 24 weeks<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 (ACR) 20 Percent (%) Improvement (ACR20 Response) at Week 24 | ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) at Week 24 | ACR50 response: ≥50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (VAS), 4) participant assessment of functional disability via a HAQ, and 5) ESR at each visit. | Week 24 | 
| Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) at Week 24 | ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (VAS), 4) participant assessment of functional disability via a HAQ, and 5) ESR at each visit. | Week 24 | 
| HAQ Disability Index (HAQ-DI) Score at Baseline and Week 24 | HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To calculate HAQ-DI the participant must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). | Baseline and Week 24 | 
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline and Week 24 | FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the 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 participants response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the health status. | Baseline and Week 24 | 
| Disease Activity Score Based on 28 Joint Count - Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline and Week 24 | DAS28-ESR calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (millimeters per hour [mm/hour]) and Patient's Global Assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity. | Baseline and Week 24 | 
| Percentage of Participants With Disease Remission at Week 24 Assessed Using DAS28-ESR | DAS28-ESR calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hour) and Patient's Global Assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 <2.6=remission. | Week 24 | 
| Percentage of Participants With Low Disease Activity at Week 24 Assessed Using DAS28-ESR | DAS28-ESR calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hour) and Patient's Global Assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 >2.6 and <3.2=low disease activity. | Week 24 | 
| Time to Onset of ACR20/50/70 Response | Time to onset of ACR 20/50/70 response was calculated as the number of weeks from the administration of the first dose of study drug until the date of first achievement of ACR 20/50/70 per criteria. | Weeks 4, 8, 12, 16, 20, and 24 |