A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate

Genentech, Inc.42 enrolled

Overview

This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

folateDRUG

Minimum of 1 mg/day oral (or folinic acid 5 mg/week)

methotrexateDRUG

15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)

methylprednisoloneDRUG

100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of RA for at least 6 months. * Inadequate response to MTX * Use of folate * If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion Exclusion Criteria: * Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16 * Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit * Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis) * Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA * Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide) * Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) * Previous treatment with Tysabri\<TM\> (natalizumab) * Previous treatment with rituximab * Previous treatment with any cell-depleting therapies, including investigational agents * Treatment with IV \&-globulin or Prosorba(R) Column within the previous 6 months * Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit * Receipt of a vaccine within 4 weeks prior to Day 1 infusion * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * Primary or secondary immunodeficiency (history of or active) * Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary disease, including any pulmonary or other condition that would preclude subject participation over the ensuing 2 years * Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) * History of recurrent significant infection or any significant episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening * History of significant cytopenias or other bone marrow disorders * History of cancer, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured) * Pregnant or nursing (breast feeding) women * Lack of peripheral venous access * Chronic daily use of narcotic analgesics * History of alcohol, drug, or chemical abuse within 6 months prior to screening

Outcomes

Primary Outcomes

Number of Participants With Either an Infection or a Grade III or IV Adverse Event (National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE], Version 3.0)

A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject's daily activities, medical intervention/therapy required and hospitalization possible. A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable. Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.

Time frame: 24 months

Secondary Outcomes

Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))

The DAS28-4(CRP) score is a measure of the subject's disease activity. DAS28-4(CRP) is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity and CRP. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity. Change from baseline at 24 months was analyzed for DAS28-4 (CRP).

Time frame: Baseline, 24 months

Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)

ACR20 response was defined as satisfying the following 3 criteria improvement from baseline: ≥ 20% in tender joint count; ≥ 20% in swollen joint count; ≥ 20% improvement from baseline in 3 of the following 5 criteria: Subject's Global Assessment of Pain Subject's Global Assessment of Disease Activity Physician's Global Assessment Subject's Self-Assessment Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) Note: The definitions of ACR50 and ACR70 are the same as ACR20, except that the 20% value in the above definition is replaced by 50% and 70% values, respectively.

Time frame: Baseline, 24 months

Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission

Data from ClinicalTrials.gov

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