A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis

NCT00299104 | Completed Phase 3 Results

• 2 other identifiers: U3373gWA17047
• Study Type: interventional
• Target: 755
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.

Conditions

Rheumatoid Arthritis

Keywords

Rituxan; MTX; RA; IMAGE; WA17047

Outcome Measures

Primary Outcomes (1)

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

  Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.

  Baseline and week 52

Secondary Outcomes (29)

• Change From Baseline in Modified Sharp Erosion Score at Week 52

  Baseline and week 52

• Percentage of Patients Without Radiographic Progression at Week 52

  Baseline, Week 52

• Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52

  Baseline, Week 52

• Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52

  Baseline and week 52

• Change From Baseline in the Modified Total Sharp Score at Week 24

  Baseline, Week 24

Study Arms (3)

Rituximab (0.5 g x 2) + Methotrexate

EXPERIMENTAL

Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6

Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: rituximab

Rituximab (1.0 g x 2) + Methotrexate

EXPERIMENTAL

Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6

Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: rituximab

Placebo + Methotrexate

PLACEBO COMPARATOR

Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.

Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: placebo

Interventions

folate DRUG

Intravenous repeating dose

Placebo + Methotrexate; Rituximab (0.5 g x 2) + Methotrexate; Rituximab (1.0 g x 2) + Methotrexate

methotrexate DRUG

Oral or parenteral repeating dose

Placebo + Methotrexate; Rituximab (0.5 g x 2) + Methotrexate; Rituximab (1.0 g x 2) + Methotrexate

methylprednisolone DRUG

Intravenous repeating dose

Placebo + Methotrexate; Rituximab (0.5 g x 2) + Methotrexate; Rituximab (1.0 g x 2) + Methotrexate

placebo DRUG

Intravenous repeating dose

Placebo + Methotrexate

rituximab DRUG

Intravenous repeating dose

Rituximab (0.5 g x 2) + Methotrexate; Rituximab (1.0 g x 2) + Methotrexate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients 18-80 years of age
• RA for ≥ 2 months;
• Receiving outpatient treatment
• Patients naive to, and considered to be candidates for, methotrexate treatment

You may not qualify if:

• Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
• Inflammatory joint disease other than RA, or other systemic autoimmune disorder
• Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16
• Surgery within 12 weeks of study
• Previous treatment with any approved or investigational biologic agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy
• Concurrent treatment with any biologic agent or DMARD other than methotrexate

Sponsors & Collaborators

• Genentech, Inc.: lead
• Hoffmann-La Roche: collaborator

Related Publications (3)

• Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W, Healy E, Hessey E, Reynard M, Shaw T. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis. 2012 Mar;71(3):351-7. doi: 10.1136/annrheumdis-2011-200170. Epub 2011 Oct 19.

  PMID: 22012969 DERIVED

• Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, Ogale S, Armstrong G, Jahreis A, Burke L, Mela C, Chen A. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res (Hoboken). 2011 May;63(5):711-20. doi: 10.1002/acr.20419.

  PMID: 21557525 DERIVED

• Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM; IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011 Jan;70(1):39-46. doi: 10.1136/ard.2010.137703. Epub 2010 Oct 11.

  PMID: 20937671 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Folic Acid; Methotrexate; Methylprednisolone; Rituximab

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)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

genentech@druginfo.com

800-821-8590

Study Officials

• Arndt Schottelius, 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: March 2, 2006
• First Posted: March 6, 2006
• Study Start: January 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: July 1, 2013
• Last Updated: July 28, 2017
• Results First Posted: August 10, 2011

Record last verified: 2017-06