A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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This open-label single-arm study will evaluate the safety, tolerability and efficacy of tocilizumab [RoActemra/Actemra] in patients with moderate to severe rheumatoid arthritis who experience an inadequate clinical response to a stable dose of non-biologic disease modifying anti-rheumatic drugs (DMARD) or anti-tumor necrosis factors (TNFs). RoActemra/Actemra will be administered as a monotherapy or in combination with DMARDs. RoActemra/Actemra will be administered as intravenous infusion at a dose of 8 mg/kg every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 24 weeks. The target sample size is 50-150 patients.

Official Title
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Multicenter, Open-Label Study to Evaluate the Safety, Tolerability and the Effect on Disease Activity of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti- TNF Therapy.

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 moderate to severe rheumatoid arthritis (DAS28 >3.2) of 6 months duration inadequate clinical response to non-biologic DMARDs or anti-TNF bodyweight </=150 kg Exclusion Criteria: rheumatic autoimmune disease or inflammatory joint disease other than RA major surgery within 8 weeks prior to screening or planned major surgery within 6 months following screening

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>* 8 mg/kg iv infusion, every 4 weeks for a total of 6 infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events | Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study. | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (>)5.1 indicated high disease activity, a score of >3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than <2.6 indicated disease remission. Week 24 is the Follow-Up visit. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline. | Weeks 4, 8, 12, 16, 20, and 24 | 
| Time to DAS28 Response by DAS28 Category | Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 <2.6), or Clinically Meaningful Improvement (change of >1.2 from baseline). | Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units | HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. | Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With Improvement in Physical Function by HAQ-DI Category | Physical function scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI <1), moderate disability (1≤ HAQ-DI <2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined. | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| HAQ-DI Score by Visit | HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| C-Reactive Protein (CRP) Values by Study Visit | CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| Erythrocyte Sedimentation Rate | ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 |