A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment (STAGE)

NCT00406419 | Terminated Phase 3 Results

• 2 other identifiers: ACT3985gWA20494
• Study Type: interventional
• Target: 1,015
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

anti-CD20; stage; CD20; RA

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24

  ACR20 is defined as 20 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).

  Week 24

• Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 48

  ACR20 is defined as 20 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).

  Week 48

• Percentage of Participants With Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a subject administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. Pre-existing conditions which worsened during the study were also reported as AEs.

  From baseline up to 8.5 years

Secondary Outcomes (23)

• Percentage of Participants With a Major Clinical Response (ACR70 for ≥ 6 Months) at Week 48

  Week 48

• Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6) at Weeks 24 and 48

  Weeks 24 and 48

• Change From Baseline in DAS28 at Weeks 24 and 48

  Weeks 24 and 48

• European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) at Weeks 24 and 48

  Weeks 24 and 48

• Percentage of Participants Achieving an ACR50 Response at Weeks 24 and 48

  Weeks 24 and 48

Study Arms (3)

Placebo × 2 IV + MTX

PLACEBO COMPARATOR

Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.

Drug: Methotrexate; Drug: Placebo

Ocrelizumab 200 mg × 2 IV + MTX

EXPERIMENTAL

Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.

Drug: Methotrexate; Drug: ocrelizumab

Ocrelizumab 500 mg × 2 IV + MTX

PLACEBO COMPARATOR

Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.

Drug: Methotrexate; Drug: ocrelizumab

Interventions

Methotrexate DRUG

Methotrexate tablet was administered orally at a dose 7.5-25 mg

Ocrelizumab 200 mg × 2 IV + MTX; Ocrelizumab 500 mg × 2 IV + MTX; Placebo × 2 IV + MTX

ocrelizumab DRUG

Ocrelizumab was administered via IV infusion at a dose specified in arm description

Ocrelizumab 200 mg × 2 IV + MTX; Ocrelizumab 500 mg × 2 IV + MTX

Placebo DRUG

Matching placebo to ocrelizumab was administered via IV infusion

Placebo × 2 IV + MTX

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
• Rheumatoid arthritis for ≥ 3 months
• Inadequate clinical response to methotrexate at a dose of 7.5-25mg/week for ≥ 12 weeks

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 (other than methotrexate)

Sponsors & Collaborators

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

Study Sites (1)

Trial Information Support Line

South San Francisco, California, 94080, United States

Location

Related Publications (2)

• 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

• 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.

  PMID: 21905001 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: F. Hoffmann-La Roche Ltd

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: November 30, 2006
• First Posted: December 4, 2006
• Study Start: December 27, 2006
• Primary Completion: October 6, 2009
• Study Completion: April 22, 2015
• Last Updated: November 27, 2020
• Results First Posted: November 27, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)