A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Non-biologic DMARDs

Study Overview
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Brief Summary
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This multicenter, open-label, single arm study will assess the safety and efficacy of RoActemra/Actemra (tocilizumab) in combination with methotrexate in patients with active rheumatoid arthritis who have an inadequate response to non-biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks for a total of 6 infusions plus methotrexate 10-25 mg orally weekly. Anticipated time on study treatment is 24 weeks.

Official Title
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An Open Label, Local, Multicenter , Phase IIIb Interventional Study to Assess the Efficacy of Tocilizumab (TCZ) in Combination With Methotrexate (MTX) in Indonesian Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Non-biologic DMARDs

Conditions
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Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Moderate to severe active rheumatoid arthritis (RA) of >/= 6 months duration Prior treatment with DMARDs for >/= 12 weeks (at stable dose for >/= 8 weeks) Inadequate clinical response to stable dose of non-biologic DMARD (either single or in combination) Exclusion Criteria: Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment Autoimmune disease other than RA History of or current inflammatory joint disease other than RA Previous treatment with any biologic drug that is used in the treatment of RA Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline Impaired liver, renal or hematologic function Active current or history of recurrent infection History of or currently active primary or secondary immunodeficiency

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: Single Arm<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 8 mg/kg iv every 4 weeks for a total of 6 infusions<br>Drug: methotrexate<br>* 10-25 mg orally weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Low Disease Activity Score | Disease Activity Score using 28-Joint Count (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/hour]) 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. 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. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve Low Disease Activity (DAS28 ≤3.2) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. DAS28 ≤3.2 = low disease activity; time to low disease activity was calculated as the time in weeks from the date of first infusion to the first achievement of DAS28 ≤3.2 | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With a Clinically Significant Improvement in DAS28 Score | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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; a clinically significant improvement in DAS28 score was defined as a reduction of at least 1.2 units. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Time to Clinically Significant Improvement in DAS28 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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; a clinically significant improvement is a reduction in DAS28 score of at least 1.2 units. Time to clinically significant improvement was determined in weeks from the date of first infusion to the date of first achievement of reduction of 1.2 units in DAS28. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. Remission was defined as DAS28 <2.6. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| Time to Achieve DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. DAS28 remission was defined as DAS28 <2.6. Time to achieve remission was calculated in weeks as the time from the date of first infusion to the date of first achieving remission. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With DAS28 <3.2 by Visit | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. DAS28 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants Achieving American College of Rheumatology (ACR) 20%, 50%, and 70% Improvement (ACR20, ACR50, or ACR70) Response | ACR20/50/70 response was defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) as well as improvement in at least 3 of the 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 acute phase response: C-reactive protein (CRP) or ESR. | Week 24 | 
| Erythrocyte Sedimentation Rate | Erythrocyte Sedimentation rate was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr. | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | 
| C-Reactive Protein Levels | CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L. | Baseline, Weeks 4, 8, 12,16, 20, and 24 |