Clinical trial NCT00243412: A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate
Official title: A Double-Blind, Randomized, Multicenter, Phase II Study of the Safety and Efficacy of Two Rituximab Regimens in Subjects With Moderate to Severe Active Rheumatoid Arthritis Receiving Stable Doses of Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rituxan
RA
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2005-10-24
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 24 months
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))
timeFrame: Baseline, 24 months
measure: Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)
timeFrame: Baseline, 24 months
measure: Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission
timeFrame: 24 months
measure: Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28-4 (DAS28-4)C-reactive Protein (CRP)
timeFrame: Baseline, 24 months
measure: Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores
timeFrame: Baseline, 24 Months
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Baseline, 24 Months
measure: Change From Baseline in Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)
timeFrame: Baseline, 24 Months
measure: DAS28-4 Erythrocyte Sedimentation Rate(ESR)
timeFrame: 24 Months
measure: Change From Baseline in Rheumatoid Factor (RF)
timeFrame: Baseline, 24 Months
measure: Change From Baseline in Cyclic Citrullinated Peptide (CCP) Antibodies/Cytokines
timeFrame: Baseline, 24 Months
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: William Reiss, Pharm.D.
role: STUDY_DIRECTOR
References: