A Multi-center, Randomized, Double-blind, Parallel Group Study of the Safety, Disease Remission and Prevention of Structural Joint Damage During Treatment With Tocilizumab (TCZ), as a Monotherapy and in Combination With Methotrexate (MTX), Versus Methotrexate in Patients With Early, Moderate to Severe Rheumatoid Arthritis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 1,162
- Locations
- 236
- Primary Endpoint
- Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24
Study Overview
Brief Summary
This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients ≥ 18 years of age.
- •Rheumatoid arthritis of ≤ 2 years duration.
- •Disease Activity Score 28 (DAS28) > 3.
- •Swollen joint count (SJC) ≥ 4 of 66 joints, tender joint count (TJC) ≥ 6 of 68 joints.
- •Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative > 1 erosion required at screening).
- •Erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or C-reactive protein (CRP) ≥ 10 mg/L at screening.
Exclusion Criteria
- •Previous treatment with tocilizumab.
- •Previous treatment with methotrexate or biologic agent.
- •Rheumatic autoimmune disease other than rheumatoid arthritis (RA).
- •History of or current inflammatory joint disease other than RA.
- •Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.
Arms & Interventions
(A) Tocilizumab 8 mg/kg + placebo to methotrexate
Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks.
Intervention: Tocilizumab (Drug)
(A) Tocilizumab 8 mg/kg + placebo to methotrexate
Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks.
Intervention: Placebo to methotrexate (Drug)
(B) Tocilizumab 8 mg/kg + methotrexate
Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Tocilizumab (Drug)
(B) Tocilizumab 8 mg/kg + methotrexate
Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Methotrexate (Drug)
(C) Tocilizumab 4 mg/kg + methotrexate
Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Tocilizumab (Drug)
(C) Tocilizumab 4 mg/kg + methotrexate
Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Methotrexate (Drug)
(D) Placebo to tocilizumab + methotrexate
Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Placebo to tocilizumab (Drug)
(D) Placebo to tocilizumab + methotrexate
Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.
Intervention: Methotrexate (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24
Time Frame: Week 24
A participant has a DAS28 remission response if their DAS28 \< 2.6. The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Secondary Outcomes
- Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52(Week 52)
- Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52(Baseline to Weeks 24 and 52)
- Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52(Baseline to Week 52)
- Change From Baseline in Modified Sharp Erosion Score at Week 52(Baseline to Week 52)
- Change From Baseline in Sharp Joint Space Narrowing Score at Week 52(Baseline to Week 52)
- Percentage of Participants With a Major Clinical Response at Week 52(Baseline to Week 52)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52(Baseline to Weeks 24 and 52)
- Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52(Baseline to Weeks 24 and 52)