Clinical trial NCT00673920: A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy
Official title: A Randomized, Double-Blind, Parallel-Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Given As a Single Infusion or Dual Infusion Compared With Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: RA
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2008-05-07
Enrollment: 314
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 to placebo, in patients with active rheumatoid arthritis who have an inadequate response to methotrexate therapy. Patients will be randomized 2:2:1 to receive 1) infusions of ocrelizumab 200mg iv on Days 1 and 15, 2) infusions of ocrelizumab 400mg iv on Day 1 and placebo iv on Day 15, or 3) infusions of placebo iv on Days 1 and 15. At the end of the placebo-controlled treatment period at 24 weeks, patients in groups 1 and 3 will be re-randomized to receive either a single infusion of 400mg iv ocrelizumab or 2 infusions of 200mg iv ocrelizumab, and group 2 will receive a second single infusion of 400mg iv ocrelizumab. All patients will receive a stable dose of concomitant methotrexate (7.5-25mg/week) throughout the study. The anticipated time on study treatment is 1-2 years. Target number of patients to be enrolled in this trial is 300.


Eligibility criteria: Inclusion criteria:

* Adult patients, ≥ 18 years of age
* Active rheumatoid arthritis
* Inadequate treatment with any DMARD other than methotrexate

Exclusion criteria:

* Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis
* Concurrent treatment with any DMARD other than methotrexate
* Previous treatment with any cell-depleting therapies
* Any surgical procedure in past 12 weeks, or planned within 48 weeks after baseline

Primary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Response
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)
timeFrame: Week 24
measure: Change in DAS28 From Baseline
timeFrame: Week 24
measure: European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)
timeFrame: Week 24
measure: Percentage of Participants Achieving an ACR50 Response
timeFrame: Week 24
measure: Percentage of Participants Achieving an ACR70 Response
timeFrame: Week 24
measure: Change From Baseline in the Individual Parameters of the ACR Core Set
timeFrame: Week 24
measure: Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration
timeFrame: Week 24
measure: Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)
timeFrame: Week 24
measure: Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score
timeFrame: Week 24
measure: Change in SF-36 Subscale and Summary Scores From Baseline
timeFrame: Week 24
measure: Change in FACIT-F Fatigue Assessment From Baseline
timeFrame: Baseline, Weeks 4, 12, and 24
measure: Percentage of Participants Achieving an ACR20 Response
timeFrame: Week 48
measure: Percentage of Participants Achieving an ACR50 Response
timeFrame: Week 48
measure: Percentage of Participants Achieving an ACR70 Response
timeFrame: Week 48
measure: Percentage of Participants Achieving DAS28 Remission (DAS28 < 2.6)
timeFrame: Week 48
measure: Cmax: Maximum Observed Serum Concentration of Ocrelizumab Following First Infusion
timeFrame: Week 24, 48
measure: Csecond: Maximum Observed Serum Concentration of Ocrelizumab Following Second Infusion
timeFrame: Day 15 of Cycles 1 and 2
Other outcomes:
Locations:
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.