Clinical trial NCT00406419: A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment (STAGE)
Official title: A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: anti-CD20
stage
CD20
RA
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2006-12-04
Enrollment: 1015
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who have had an inadequate response to methotrexate. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab or 500mg of i.v. ocrelizumab on Days 1 and 15. A repeat course of i.v. treatment will be administered at Weeks 24 and 26. All patients will receive 7.5mg - 25mg/week concomitant methotrexate at a stable dose. The anticipated time on study treatment is 1-2 years. Target sample size is 1000.


Eligibility criteria: Inclusion criteria:

* Adult patients, ≥18 years of age
* Rheumatoid arthritis for ≥ 3 months
* Inadequate clinical response to methotrexate at a dose of 7.5-25mg/week for ≥ 12 weeks

Exclusion criteria:

* Rheumatic autoimmune disease or inflammatory joint disease, other than RA
* Prior receipt of any biologic therapy for RA
* Concurrent treatment with any DMARD (other than methotrexate)

Primary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From baseline up to 8.5 years
Secondary outcomes:
measure: Percentage of Participants With a Major Clinical Response (ACR70 for ≥ 6 Months) at Week 48
timeFrame: Week 48
measure: Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6) at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Change From Baseline in DAS28 at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Percentage of Participants Achieving an ACR50 Response at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Percentage of Participants Achieving an ACR70 Response at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Percent Change From Baseline in Swollen Joint Count (SJC) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Tender Joint Count (TJC) at Weeks 24 and 48
timeFrame: Baseline, Weeks 24, 48
measure: Change From Baseline in Patient's Pain Visual Analogue Scale (VAS) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Physician's Global VAS at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Patient's Global VAS at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in C-Reactive Protein (CRP) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in the Modified Total Sharp Score (mTSS) at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Modified Erosion Score at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Modified Joint Space Narrowing Score at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Percentage of Participants Without Radiographic Progression Defined as Change in mTSS ≤ 0 at Weeks 24 and 48
timeFrame: Weeks 24, 48
measure: Percentage of Participants With a Reduction in Modified Total Sharp Score (mTSS) From Baseline at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score at Weeks 24 and
timeFrame: Week 24, 48
measure: Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Fatigue Assessment at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
measure: Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48
timeFrame: Baseline, Week 24, 48
Other outcomes:
Locations:
city: South San Francisco
country: United States
facility: Trial Information Support Line
state: California
Study officials:
affiliation: Genentech, Inc.
name: Wolfgang Dummer, M.D.
role: STUDY_DIRECTOR
References:
citation: Emery P, Rigby W, Tak PP, Dorner T, Olech E, Martin C, Millar L, Travers H, Fisheleva E. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS One. 2014 Feb 3;9(2):e87379. doi: 10.1371/journal.pone.0087379. eCollection 2014.
citation: Rigby W, Tony HP, Oelke K, Combe B, Laster A, von Muhlen CA, Fisheleva E, Martin C, Travers H, Dummer W. Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum. 2012 Feb;64(2):350-9. doi: 10.1002/art.33317.