A Study of the Safety of Rituximab in Combination With Other Anti-Rheumatic Drugs in Subjects With Active Rheumatoid Arthritis

• Status: Completed
• Trial end date: 2013-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase III, open-label study of a total of approximately 560 subjects with active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Enrollment in the study was conducted in two stages. In Stage I of the study, approximately 400 subjects receiving non-biological DMARDs (with the exception of methotrexate [MTX] monotherapy or MTX and leflunomide combination therapy) were enrolled. In Stage II of the study, approximately 160 subjects receiving a Federal Drug Administration-approved biological DMARD at the time of screening were enrolled.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Collaborator: Biogen
• Treatments: Anti-Inflammatory Agents; Antirheumatic Agents; Rituximab

Criteria

Inclusion Criteria (Stage I):

• Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active rheumatoid arthritis (RA) for ≥ 6 months

• Receiving treatment for RA on an outpatient basis

• Have had an inadequate response to at least one non-biological disease-modifying anti-rheumatic drug (DMARD) and have been receiving this DMARD(s) for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline

• Demonstrated tolerability to currently prescribed DMARDs

• If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to the first day of treatment with rituximab (Day 1)

• Use of one nonsteroidal anti-inflammatory drug (NSAID) is permitted if the dose is stable for ≥ 2 weeks prior to Day 1

Exclusion Criteria (Stage I):

• Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)

• Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis

• History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder

• Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years

• Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of enrollment

• Lack of peripheral venous access

• 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 that, in the investigator's opinion, would preclude subject participation

• Primary or secondary immunodeficiency (history of or currently active), including known history of human immunodeficiency virus (HIV) infection

• Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline

• History of medically significant opportunistic infection

• History of serious recurrent or chronic infection

• History of deep space/tissue infection within 52 weeks prior to baseline

• History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)

• History of significant cytopenias or other bone marrow disorders

• History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline

• Pregnancy or lactation

• Neuropathies and neurovasculopathies that might interfere with pain evaluation

• Methotrexate (MTX) monotherapy at the time of screening

• Concurrent treatment with MTX and leflunomide in combination

• Concurrent treatment with any biologic agent

• Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol

• History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins

• Previous treatment with an anti-α4 integrin agent

• Previous treatment with any cell-depleting therapies, including investigational agents

• Receipt of any vaccine within 28 days prior to baseline

• Intolerance or contraindications to IV corticosteroids

• Receipt of IV immunoglobulin (IVIG) or Prosorbacolumn within 6 months prior to baseline

• Any previous treatment with rituximab

• Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

Inclusion Criteria (Stage II):

• Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active RA for ≥ 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of RA

• Receiving treatment for RA on an outpatient basis

• Have had an inadequate response to at least one biologic DMARD and have been receiving this agent at screening and for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline

• Have demonstrated tolerability to currently prescribed DMARDs/biologics

• If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to baseline

• Use of one NSAID is permitted if the dose is stable for ≥ 2 weeks prior to baseline

Exclusion Criteria (Stage II):

• Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)

• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis

• History of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder

• Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years

• Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of randomization

• Lack of peripheral venous access

• 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 that, in the investigator's opinion, would preclude subject participation

• Primary or secondary immunodeficiency (history of or currently active), including known history of HIV infection

• Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline

• History of medically significant opportunistic infection

• History of serious recurrent or chronic infection

• History of deep space/tissue infection within 52 weeks prior to baseline

• History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)

• History of significant cytopenias or other bone marrow disorders

• History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline

• Pregnancy or lactation

• Neuropathies and neurovasculopathies that might interfere with pain evaluation

• Infliximab monotherapy at the time of screening (infliximab should be in combination with MTX)

• Concurrent treatment with MTX and leflunomide in combination

• Concurrent treatment with more than one biologic agent

• Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol

• History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins

• Previous treatment with an anti-α4 integrin agent

• Previous treatment with any cell-depleting therapies

• Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (whichever is the longer)

• Receipt of any vaccine within 28 days prior to baseline

• Intolerance or contraindications to IV corticosteroids

• Receipt of IVIG or Prosorba column within 6 months prior to baseline

• Any previous treatment with rituximab

• Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

• Positive purified protein derivative (PPD) skin test not adequately treated according to Center for Disease Control (CDC) guidelines