A Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
NCT ID: NCT00282308
Last Updated: 2017-08-10
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
103 participants
INTERVENTIONAL
2006-01-23
2012-05-28
Brief Summary
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Detailed Description
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Group A
Group A patients received rituximab 1000 mg intravenously (IV) on Days 3 and 17 of the 36 week treatment period.
At Day 1 and at Week 24, patients received an intradermal injection of 0.1 mL of C. albicans on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin).
At Week 24, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) intramuscular (IM) injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed vaccine.
At Week 28, patients received an IM injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal serotypes were measured at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after administration of the pneumococcal vaccine.
At Weeks 32 and 33, patients received subcutaneous (SC) keyhole limpet hemocyanin 1 mg. Serum anti-keyhole limpet hemocyanin antibody levels were measured at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin.
Samples were obtained for the determination of serum rituximab concentration (pharmacokinetics), peripheral blood CD19 counts (pharmacodynamics), and the presence of human anti-chimeric antibodies from all patients in Group A.
Group A patients completed the treatment period at Week 36 and, if qualified, had the option of entering the optional extension re-treatment period. Patients who did not qualify for or who did not choose to receive the optional extension re-treatment entered the approximately 1-year safety follow-up period. After the safety follow-up period, patients who remained peripherally CD19-positive B-cell depleted entered the B-cell follow-up period where they were followed every 12 weeks until their peripheral CD19-positive B cells returned to baseline values or the lower limit of normal, whichever was lower.
Group B
Because the immune response to vaccines was not likely to be influenced by the knowledge of treatment assignment or the time-of-year administration, vaccinations of Group B patients were administered sooner than in the Group A 36 week treatment period.
At Day 1 and at Week 12, patients received an intradermal injection of 0.1 mL of C. albicans on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin).
On Day 1, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) IM injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed vaccine.
At Week 4, patients received an IM injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal serotypes were measured at Day 1, and immediately prior to and 4 weeks after administration of the pneumococcal vaccine.
At Weeks 8 and 9, patients received SC keyhole limpet hemocyanin 1 mg. Serum anti-keyhole limpet hemocyanin antibody levels were measured at Day 1, and immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin.
Upon completion of the Week 12 visit, Group B patients with active rheumatic arthritis, defined as a swollen joint count (SJC) ≥ 4 (66 joint count) and a tender joint count (TJC) ≥ 6 (68 joint count) were eligible for treatment with 2 infusions of rituximab 1000 mg IV, 14 days apart. Patients received the first infusion of rituximab within 2 weeks after completing the Week 12 visit and after the second C. albicans skin test had been read. Patients received methylprednisolone 100 mg IV before each infusion of rituximab.
Group B patients who received treatment with rituximab completed the treatment period through Week 36 and, if qualified, had the option of entering the optional extension re-treatment period. Patients who did not qualify for or who did not choose to receive the optional extension re-treatment entered the approximately 1-year safety follow-up period. After the safety follow-up period, patients who remained peripherally CD19-positive B-cell depleted entered the B-cell follow-up period where they were followed every 12 weeks until their peripheral CD19-positive B cells returned to baseline values or the lower limit of normal, whichever was lower.
Group B patients who did not qualify for and/or did not choose treatment with rituximab completed the study at the end of the primary study period (Week 12).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Rituximab
Rituximab was supplied in single-use vials.
Methotrexate
Methylprednisone
Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab.
C. albicans
Patients received an intradermal injection of C. albicans (0.1 mL) on the volar surface of the forearm.
Tetanus toxoid adsorbed booster vaccine
Patients received an intramuscular injection of the tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) in the deltoid muscle.
23-valent pneumococcal polysaccharide vaccine
Patients received an intramuscular injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle.
Keyhole limpet hemocyanin
Patients received a subcutaneous injection of keyhole limpet hemocyanin (1 mg)
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Methotrexate
C. albicans
Patients received an intradermal injection of C. albicans (0.1 mL) on the volar surface of the forearm.
Tetanus toxoid adsorbed booster vaccine
Patients received an intramuscular injection of the tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) in the deltoid muscle.
23-valent pneumococcal polysaccharide vaccine
Patients received an intramuscular injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle.
Keyhole limpet hemocyanin
Patients received a subcutaneous injection of keyhole limpet hemocyanin (1 mg)
Interventions
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Rituximab
Rituximab was supplied in single-use vials.
Methotrexate
Methylprednisone
Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab.
C. albicans
Patients received an intradermal injection of C. albicans (0.1 mL) on the volar surface of the forearm.
Tetanus toxoid adsorbed booster vaccine
Patients received an intramuscular injection of the tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) in the deltoid muscle.
23-valent pneumococcal polysaccharide vaccine
Patients received an intramuscular injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle.
Keyhole limpet hemocyanin
Patients received a subcutaneous injection of keyhole limpet hemocyanin (1 mg)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of rheumatoid arthritis (RA) for at least 6 months.
* Receiving treatment for RA on an outpatient basis.
* Use of methotrexate (MTX) at a dose of 10-25 mg/wk (oral \[PO\] or subcutaneous \[SC\]) for at least 12 weeks prior to Day 1, with the dose stable during the last 4 weeks prior to Day 1 (first day of the treatment period).
* If taking a background corticosteroid, use of the corticosteroid must be for at least 12 weeks prior to Day 1 at a stable dose during the last 4 weeks prior to Day 1.
* If taking one non-steroidal anti-inflammatory drug (NSAID), use of a stable dose for at least 2 weeks prior to Day 1.
Exclusion Criteria
18 Years
65 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Ariella Kelman, M.D.
Role: STUDY_DIRECTOR
Genentech, Inc.
Locations
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Univ of Alabama at Birmingham
Birmingham, Alabama, United States
Arizona Arthritis & Rheumatology Research, Pllc
Paradise Valley, Arizona, United States
Sun Valley Arthritis Center
Peoria, Arizona, United States
Desert Medical Advances
Palm Desert, California, United States
Inland Rheumatology; Clinical Trials, Inc.
Upland, California, United States
Arthritis Associates of South Florida
Delray Beach, Florida, United States
The Arthritis Center
Palm Harbor, Florida, United States
Center For Arthritis; Research Dept
South Miami, Florida, United States
Intermountain Orthopaedics
Boise, Idaho, United States
Northwestern University
Chicago, Illinois, United States
Univ of Chicago
Chicago, Illinois, United States
Evanston Northwestern Healthcare
Evanston, Illinois, United States
Springfield Clinic
Springfield, Illinois, United States
Kentuckiana Center For Better Bone & Joint Healthx
Louisville, Kentucky, United States
Clinical Research Network
Slidell, Louisiana, United States
Johns Hopkins University; Rheumatology
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Rheumatology, P.C.; Medical Arts Building
Kalamazoo, Michigan, United States
Borgess Research Institute
Kalamazoo, Michigan, United States
Justus Fiechtner MD - PP
Lansing, Michigan, United States
Center for Rheumatology, State Uni. of New York
Albany, New York, United States
Aair Research Center
Rochester, New York, United States
University of Rochester - Strong Memorial Hospital
Rochester, New York, United States
Physicians East Pa
Greenville, North Carolina, United States
Health Research of Oklahoma, Llc
Oklahoma City, Oklahoma, United States
Oregon Health Sciences Uni
Portland, Oregon, United States
Altoona Arthritis & Osteo Center
Duncansville, Pennsylvania, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Rheumatology Associates
Charleston, South Carolina, United States
Medical University of S. Carolina
Charleston, South Carolina, United States
Arthritis Associates
Hixson, Tennessee, United States
Arthritis Care & Diagnostic Center
Dallas, Texas, United States
Arthritis Clinic of Northern Virginia
Arlington, Virginia, United States
Arthritis Northwest, Spokane
Spokane, Washington, United States
Countries
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References
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Bingham CO 3rd, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010 Jan;62(1):64-74. doi: 10.1002/art.25034.
Other Identifiers
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U3374g
Identifier Type: -
Identifier Source: org_study_id
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