A Study of Retreatment With Rituximab in Patients With Rheumatoid Arthritis Receiving Background Methotrexate

NCT00266227 | Completed Phase 3 Results

• 1 other identifier: U3384g
• Study Type: interventional
• Target: 559
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy of retreatment with rituximab in subjects with active rheumatoid arthritis (RA) who are receiving Methotrexate (MTX).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Retreated Subjects With an American College of Rheumatology 20% (ACR20) Response at Week 48 Relative to Baseline

  ACR20 response was defined as a ≥ 20% improvement compared with baseline in both tender joint count (TJC) \[68 joints\] and swollen joint count (SJC) \[66 joints\] as well as a ≥ 20% improvement in three of five additional measurements: 1) Physician's Global Assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[visual analog scale: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) erythrocyte sedimentation rate.

  48 Weeks

Secondary Outcomes (19)

• Retreated Subjects With American College of Rheumatology 50% (ACR50) Response and American College of Rheumatology 70% (ACR70) Response at Week 48 Relative to Baseline

  Baseline, Week 48

• Change From Baseline in the Disease Activity Score Using 28 Joint Counts (DAS28-ESR) at Week 48

  48 weeks

• Change From Baseline in Disease Activity Score (DAS28-CRP) at Week 48

  Baseline, Week 48

• Percentage of Retreated Subjects With a European League Against Rheumatism (EULAR) Response at Week 48

  Baseline, Week 48

• Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Swollen Joint Count at Week 48

  Baseline, Week 48

Study Arms (2)

Arm A: Rituximab Retreatment

EXPERIMENTAL

1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.

Drug: rituximab; Drug: methotrexate; Drug: folate

Arm B: Placebo Retreatment

PLACEBO COMPARATOR

1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.

Drug: placebo; Drug: methotrexate; Drug: folate

Interventions

placebo DRUG

Intravenous repeating dose

Arm B: Placebo Retreatment

rituximab DRUG

Intravenous repeating dose

Arm A: Rituximab Retreatment

methotrexate DRUG

Oral or parenteral repeating dose

Arm A: Rituximab Retreatment; Arm B: Placebo Retreatment

folate DRUG

Intravenous repeating dose

Arm A: Rituximab Retreatment; Arm B: Placebo Retreatment

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Ability and willingness to comply with the requirements of the study protocol
• Age 18-80 years
• Diagnosis of RA for at least 6 months
• Receiving treatment for RA on an outpatient basis
• Documented moderate to severe active RA activity at screening and Day 1
• Documented inadequate response to previous or current treatment with one or more of the following: etanercept, infliximab, and/or adalimumab because of toxicity or inadequate efficacy
• Use of MTX 10-25 mg/wk for ≥ 12 weeks prior to Day 1 at a stable dose for ≥ 4 weeks
• Willingness to receive oral folic acid
• If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to Day 1
• Use of one NSAID is permitted if the dose is stable for ≥ 2 weeks prior to Day 1
• For men and women of reproductive potential, willingness to use a reliable means of contraception for ≥ 30 days prior to Day 1 and for the study duration or the duration that the subject's peripheral CD19 B cells are depleted, whichever is longer

You may not qualify if:

• Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Secondary Sjogren's syndrome with RA is permitted.
• History of or current inflammatory joint disease other than RA or other systemic rheumatic disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, or overlap syndrome)
• History of deep space/tissue infection within 52 weeks prior to Day 1
• Diagnosis of juvenile idiopathic arthritis (JIA), juvenile rheumatoid arthritis (JRA), and/or RA before age 16
• Functional Class IV, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement), within 12 weeks prior to Day 1 or planned within 48 weeks after Day 1
• Known hypersensitivity to any component of a humanized or murine monoclonal antibody
• Receipt of any vaccination within 4 weeks prior to Day 1
• Significant cardiac or pulmonary disease, including obstructive pulmonary disease
• Evidence of significant uncontrolled concomitant disease, such as, but not limited to nervous system, renal, hepatic, endocrine, or gastrointestinal disorders
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease but excluding fungal infections of the nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Day 1 or oral antibiotics within 2 weeks of Day 1
• History of serious recurrent or chronic infection (a chest X-ray will be performed at screening if one has not been performed within 12 weeks of screening that showed no clinically significant abnormality)
• History of or currently active primary or secondary immunodeficiency, including HIV infection
• History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that has been excised and cured)
• History of significant cytopenias or other bone marrow disorders

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; Methotrexate; Folic Acid

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)

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

Results Point of Contact

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

800-821-8590

Study Officials

• Anshu Vashishtha, MD PhD

  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: December 14, 2005
• First Posted: December 16, 2005
• Study Start: January 1, 2006
• Primary Completion: October 1, 2007
• Last Updated: October 25, 2013
• Results First Posted: May 25, 2009

Record last verified: 2013-09