A Randomized, Double Blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With DMARD Therapy, in Patients With Active Rheumatoid Arthritis and Inadequate Response to Current DMARD Therapy
Overview
- Phase
- Phase 3
- Intervention
- tocilizumab [RoActemra/Actemra]
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 209
- Locations
- 9
- Primary Endpoint
- Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •adult patients, 18-70 years of age;
- •rheumatoid arthritis for \>= 6 months;
- •receiving permitted DMARDs, at a stable dose, for \>= 8 weeks prior to baseline;
- •current inadequate clinical response to DMARDs.
Exclusion Criteria
- •major surgery, including joint surgery, within 8 weeks before entering study, or planned major surgery within 6 months following randomization;
- •rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
- •unsuccessful treatment with an anti-TNF agent;
- •previous treatment with tocilizumab.
Arms & Interventions
1
Intervention: tocilizumab [RoActemra/Actemra]
2
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24
Time Frame: Week 24
To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward \[LOCF\]).
Secondary Outcomes
- Change in Participant's Global Assessment of Pain From Baseline to Week 24(Baseline and Week 24)
- Number of Participants Who Received Escape Therapy(24 Weeks)
- Change in Tender and Swollen Joint Counts From Baseline to Week 24(Baseline and Week 24)
- Change in C-Reactive Protein From Baseline to Week 24(Baseline and Week 24)
- Change in ESR From Baseline to Week 24(Baseline and Week 24)
- Mean Rheumatoid Factor at Baseline and Week 24(Baseline and 24 Weeks)
- Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24(Baseline and 24 Weeks)
- Percentage of Participants With ACR50 and ACR70 Responses at Week 24(Week 24)
- Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24(Baseline and Week 24)
- Percentage of Participants With Low Disease Activity and in Clinical Remission(Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24)
- Change in Hemoglobin From Baseline to Week 24(Baseline and 24 Weeks)
- Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24(Baseline and Week 24)
- Percentage of Participants With ACR20 Response by First Week of Onset(Weeks 2, 4, 8, 12, 16, 20, and 24)
- Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score(Baseline and Week 24)
- Time to First Low Disease Activity(Weeks 2, 4, 8, 12, 16, 20, and 24)
- Time to First Remission(Weeks 2, 4, 8, 12, 16, 20, and 24)