A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

NCT00673920 | Terminated Phase 3 Results

• 2 other identifiers: ACT4394gWA20496
• Study Type: interventional
• Target: 314
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Keywords

RA

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With American College of Rheumatology (ACR) 20 Response

  ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

  Week 24

Secondary Outcomes (17)

• Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)

  Week 24

• Change in DAS28 From Baseline

  Week 24

• European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)

  Week 24

• Percentage of Participants Achieving an ACR50 Response

  Week 24

• Percentage of Participants Achieving an ACR70 Response

  Week 24

Study Arms (8)

Placebo

PLACEBO COMPARATOR

Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)

Drug: Methotrexate; Drug: Placebo

Ocrelizumab 400mg

EXPERIMENTAL

Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.

Drug: Methotrexate; Drug: Ocrelizumab

Ocrelizumab 200mg

EXPERIMENTAL

Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.

Drug: Methotrexate; Drug: Ocrelizumab

Ocrelizumab 200mg/ Ocrelizumab 200mg

EXPERIMENTAL

Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2

Drug: Methotrexate; Drug: Ocrelizumab

Ocrelizumab 200mg/ Ocrelizumab 400mg

EXPERIMENTAL

Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

Drug: Methotrexate; Drug: Ocrelizumab

Ocrelizumab 400mg/ Ocrelizumab 400mg

EXPERIMENTAL

Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

Drug: Methotrexate; Drug: Ocrelizumab

Placebo/ Ocrelizumab 200mg

EXPERIMENTAL

Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2

Drug: Methotrexate; Drug: Ocrelizumab; Drug: Placebo

Placebo/ Ocrelizumab 400mg

EXPERIMENTAL

Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

Drug: Methotrexate; Drug: Ocrelizumab; Drug: Placebo

Interventions

Methotrexate DRUG

Oral or parenteral repeating dose

Ocrelizumab 200mg; Ocrelizumab 200mg/ Ocrelizumab 200mg; Ocrelizumab 200mg/ Ocrelizumab 400mg; Ocrelizumab 400mg; Ocrelizumab 400mg/ Ocrelizumab 400mg; Placebo; Placebo/ Ocrelizumab 200mg; Placebo/ Ocrelizumab 400mg

Ocrelizumab DRUG

Ocrelizumab was administered as a slow intravenous (iv) infusion during each course as either 200 mg on Day 1 and Day 15 (OCR 200×2) or as 400 mg given on Day 1 (OCR 400×1). Ocrelizumab was administered in combination with Methotrexate.

Ocrelizumab 200mg; Ocrelizumab 200mg/ Ocrelizumab 200mg; Ocrelizumab 200mg/ Ocrelizumab 400mg; Ocrelizumab 400mg; Ocrelizumab 400mg/ Ocrelizumab 400mg; Placebo/ Ocrelizumab 200mg; Placebo/ Ocrelizumab 400mg

Placebo DRUG

Intravenous repeating dose

Placebo; Placebo/ Ocrelizumab 200mg; Placebo/ Ocrelizumab 400mg

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

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: May 5, 2008
• First Posted: May 7, 2008
• Study Start: April 24, 2008
• Primary Completion: October 26, 2009
• Study Completion: October 26, 2009
• Last Updated: December 4, 2020
• Results First Posted: December 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share