Status:
COMPLETED
A Study of the Safety of Rituximab in Combination With Other Anti-Rheumatic Drugs in Subjects With Active Rheumatoid Arthritis
Lead Sponsor:
Genentech, Inc.
Collaborating Sponsors:
Biogen
Conditions:
Rheumatoid Arthritis
Eligibility:
All Genders
18-80 years
Phase:
PHASE3
Brief 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...
Eligibility Criteria
Inclusion
- 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 Prosorba\<TM\> 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
- 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\<TM\> 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
Exclusion
Key Trial Info
Start Date :
January 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 1 2013
Estimated Enrollment :
578 Patients enrolled
Trial Details
Trial ID
NCT00443651
Start Date
January 1 2007
End Date
February 1 2013
Last Update
April 17 2017
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