A Study of Ocrelizumab in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Are Naive to Methotrexate (FILM)

NCT00485589 | Terminated Phase 3 Results

• 2 other identifiers: ACT3984gWA20497
• Study Type: interventional
• Target: 613
• Locations: 0 countries
• Sites: N/A

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 are naive to methotrexate. Patients will be randomized to receive placebo, ocrelizumab 200mg i.v. or ocrelizumab 500mg i.v. on Days 1 and 15. Repeat courses of i.v. treatment will be administered at weeks 24, 52 and 76. All patients will receive concomitant methotrexate (7.5 mg escalating to 20mg p.o. weekly). The anticipated time on study treatment is 2+ years, and the target sample size is 500+ individuals.

Conditions

Rheumatoid Arthritis

Keywords

FILM; RA; anti-CD20; CD20

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52

  The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.

  Baseline to Week 52

Secondary Outcomes (3)

• Percentage of Participants Without Radiographic Progression (RP) at Week 52

  Week 52

• Percentage of Participants With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52

  Baseline to Week 52

• Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52

  Week 24 and Week 52

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Placebo

Ocrelizumab 200 mg

EXPERIMENTAL

Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Methotrexate; Drug: Ocrelizumab

Ocrelizumab 500 mg

EXPERIMENTAL

Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Methotrexate; Drug: Ocrelizumab

Interventions

Methotrexate DRUG

Oral repeating dose

Ocrelizumab 200 mg; Ocrelizumab 500 mg

Ocrelizumab DRUG

Intravenous repeating dose

Ocrelizumab 200 mg; Ocrelizumab 500 mg

Placebo DRUG

Intravenous repeating dose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Rheumatoid arthritis for 3 months-5 years
• Naive to methotrexate
• If receiving steroids or NSAIDs, must be on a stable dose for 4 weeks prior to baseline

You may not qualify if:

• Rheumatic autoimmune disease or inflammatory joint disease other than RA
• Prior receipt of any biologic therapy for RA
• Concurrent treatment with any DMARD

Sponsors & Collaborators

• Genentech, Inc.: lead
• Roche Pharma AG: collaborator

Related Publications (1)

• 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.

  PMID: 24498318 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; ocrelizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was terminated prematurely by the sponsors before all patients could reach the time point for primary analysis at Week 104. No patient received any further infusions of study medication.

Results Point of Contact

• Title: Medical Communications
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

41 616878333

Study Officials

• Wolfgang Dummer, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2007
• First Posted: June 13, 2007
• Study Start: June 11, 2007
• Primary Completion: January 29, 2010
• Study Completion: August 29, 2013
• Last Updated: November 3, 2020
• Results First Posted: November 3, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share