Phase 3
N=1,162
A Study of Tocilizumab as Monotherapy and in Combination With Methotrexate Versus Methotrexate in Patients With Early Moderate to Severe Rheumatoid Arthritis
Rheumatoid Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT01007435 ↗Enrolled (actual)
1,162
Serious AEs
9.5%
Results posted
Jul 2013
Primary outcome: Primary: Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 — 15.0; 31.9; 44.8; 38.7 Percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tocilizumab (Drug); Placebo to tocilizumab (Drug); Methotrexate (Drug); Placebo to methotrexate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- May 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 |
15.0; 31.9; 44.8; 38.7 | <0.0001 sig |
| SECONDARY Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 |
19.5; 34.0; 49.0; 39.4 | — |
| SECONDARY 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 |
65.2; 73.6; 74.5; 70.2; 43.2; 47.9 | — |
| SECONDARY Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 |
1.14; 0.42; 0.08; 0.26 | — |
| SECONDARY Change From Baseline in Modified Sharp Erosion Score at Week 52 |
0.63; 0.25; 0.05; 0.15 | — |
| SECONDARY Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 |
0.51; 0.17; 0.03; 0.11 | — |
| SECONDARY Percentage of Participants With a Major Clinical Response at Week 52 |
16; 22; 31; 22 | — |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 |
-0.71; -0.92; -0.91; -0.82; -0.76; -1.00 | — |
| SECONDARY Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 |
9.35; 11.33; 12.13; 10.75; 10.72; 12.27 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Adult patients ≥ 18 years of age.
- Rheumatoid arthritis of ≤ 2 years duration.
- Disease Activity Score 28 (DAS28) > 3.2.
- 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.
Data sourced from ClinicalTrials.gov (NCT01007435). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.