A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus
- Conditions
- Lupus Erythematosus, Systemic
- Interventions
- Registration Number
- NCT00137969
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab compared with placebo when combined with a single stable background immunosuppressive medication in subjects with moderate to severe systemic lupus erythematosus (SLE). The primary efficacy endpoint of the trial will be evaluated at 52 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 262
- Diagnosis of systemic lupus erythematosus (SLE).
- Active disease at screening.
- Stable use of one immunosuppressive drug.
- Use of an antimalarial drug.
- For subjects of reproductive potential (males and females), use of a reliable means of contraception throughout their study participation.
- Unstable patients with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.
- Active moderate to severe glomerulonephritis.
- Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.
- Lack of peripheral venous access.
- Pregnant women or nursing (breast feeding) mothers.
- History of severe, allergic, or anaphylactic reactions to humanized or murine monoclonal antibodies.
- Significant, uncontrolled medical disease in any organ system not related to SLE that in the investigator's opinion would preclude subject participation.
- Concomitant conditions that require oral or systemic corticosteroid use.
- Known human immunodeficiency virus (HIV) infection.
- Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics.
- History of deep space infection.
- History of serious recurrent or chronic infection.
- History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ.
- Active alcohol or drug abuse, or history of alcohol or drug abuse.
- Major surgery.
- Previous treatment with CAMPATH-1H antibody.
- Previous treatment with any B cell-targeted therapy.
- Treatment with any investigational agent within 28 days of screening (Day -7) or 5 half-lives of the investigational drug (whichever is longer).
- Receipt of a live vaccine within 28 days prior to screening.
- Intolerance or contraindication to oral or IV corticosteroids.
- Use of a new immunosuppressive drug prior to screening or change in dose of ongoing immunosuppressive drug prior to screening.
- Prednisone dose of ≥ 1 mg/kg/day prior to screening.
- Treatment with cyclophosphamide or a calcineurin inhibitor.
- Treatment with a second immunosuppressive or immunomodulatory drug.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab 1000 mg + prednisone Diphenhydramine Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Rituximab 1000 mg + prednisone Rituximab Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Placebo + prednisone Placebo Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Placebo + prednisone Acetaminophen Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Rituximab 1000 mg + prednisone Prednisone Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Rituximab 1000 mg + prednisone Acetaminophen Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Placebo + prednisone Prednisone Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion. Placebo + prednisone Diphenhydramine Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
- Primary Outcome Measures
Name Time Method Number of Participants Who Achieved a Major Clinical Response (MCR), Partial Clinical Response (PCR), or Nonclinical Response (NCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over The 52-week Treatment Period From baseline to 52 weeks The BILAG Index measures clinical disease activity in Systemic Lupus Erythematosus (SLE). A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24; PCR = participants who achieved BILAG C score or better at 24 wks and maintained response without a flare for 16 consecutive weeks, or maximum of one BILAG B score at 24 weeks and maintained response without a flare to 52 wks, or maximum of 2 BILAG B scores at 24 wks without development of BILAG scores of A or B until Week 52 if the baseline BILAG score was 1A+\>=2Bs, or\>=2 As, or\>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6.
- Secondary Outcome Measures
Name Time Method Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period From baseline to 52 weeks The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. The AUCMB of BILAG Score Over 52 Weeks was calculated as: 1. Calculate the AUC of the BILAG global score versus time (in days) by 52 weeks. 2. Calculate the Time-Adjusted AUC by dividing the AUC by the number of days a patient was on the study. 3. Minus the Time-Adjusted AUC by the baseline BILAG global score
Number of Participants Who Achieved an MCR (Excluding PCR) From baseline to 52 weeks The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24. PCR = participants who achieved BILAG C score or better at 24 wks and maintained response without a flare for 16 consecutive weeks, or maximum of one BILAG B score at 24 weeks and maintained response without a flare to 52 wks, or maximum of 2 BILAG B scores at 24 wks without development of BILAG scores of A or B until Week 52 if the baseline BILAG score was 1A+\>=2Bs, or\>=2 As, or\>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6.
Number of Participants Who Achieved a PCR (Including MCR) From baseline to 52 Weeks The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. PCR = participants who achieved BILAG C score or better at 24 wks and maintained response without a flare for 16 consecutive weeks, or maximum of one BILAG B score at 24 weeks and maintained response without a flare to 52 wks, or maximum of 2 BILAG B scores at 24 wks without development of BILAG scores of A or B until Week 52 if the baseline BILAG score was 1A+\>=2Bs, or\>=2 As, or\>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6. MCR = participants who achieved BILAG C or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24.
Number of Participants Who Achieved a BILAG C or Better in All Domains 24 weeks The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains.
Time to First Moderate or Severe Flare 52 weeks The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. A severe flare = participants had BILAG A score(s) present in one or more domains or BILAG B scores present in three or more domains at the same visit following a visit of inactive disease state defined above. A moderate flare = participants had only BILAG B scores present in two domains at the same visit following a visit of inactive disease state.
Change in SLE Expanded Health Survey Physical Function Score From Baseline From baseline to 52 weeks Short Form (36) with additional questions specific to lupus (scale = 0-100; with 100 representing the highest level of functioning possible) to measure the ability of rituximab to improve quality of life. A positive value for this outcome measure indicates that symptoms have improved.
Number of Participants Who Achieved an MCR in The ITT Population From Weeks 24 to 52 The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24.
Trial Locations
- Locations (65)
Univ of Calif., Los Angeles; Rheumatology
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Emory Uni ; Division of Rheumatology
🇺🇸Atlanta, Georgia, United States
Univ of California, San Diego
🇺🇸La Jolla, California, United States
Tri-State Arth & Rheum Center
🇺🇸Evansville, Indiana, United States
Buffalo Rheumatology Associates
🇺🇸Orchard Park, New York, United States
Arizona Arthritis & Rheumatology Research, Pllc
🇺🇸Paradise Valley, Arizona, United States
Arthritis & Rheumatism; Disease Specialities
🇺🇸Aventura, Florida, United States
Family Arthritis Center
🇺🇸Jupiter, Florida, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
NYU-Hosp for Joint Diseases; Rheum and Med
🇺🇸New York, New York, United States
Washington University; Rheumatology Division
🇺🇸Saint Louis, Missouri, United States
Johns Hopkins Uni
🇺🇸Baltimore, Maryland, United States
Center for Rheumatology, State Uni. of New York
🇺🇸Albany, New York, United States
SUNY Downstate Medical Center.
🇺🇸Brooklyn, New York, United States
Long Island Osteo/Arth Center
🇺🇸Plainview, New York, United States
University of Rochester - Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Texas Research Center
🇺🇸Sugar Land, Texas, United States
Oklahoma Center For Arthritis Therapy & Research
🇺🇸Tulsa, Oklahoma, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Arthritis & Osteoporosis Associates, LLP
🇺🇸Lubbock, Texas, United States
East Penn Rheumatology Associates, Pc
🇺🇸Bethlehem, Pennsylvania, United States
Arthritis Centers of Texas
🇺🇸Dallas, Texas, United States
University of Virginia Med Ctr; Div of Ped Respiratory Med
🇺🇸Charlottesville, Virginia, United States
St. Joseph'S Health Care Centre
🇨🇦London, Ontario, Canada
Univ of Manitoba, Health Scien; Arthritis Centre
🇨🇦Winnipeg, Manitoba, Canada
Metroplex Clinical Research
🇺🇸Dallas, Texas, United States
Uni of Pennslyvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Ohio State University; Division of Nephrology
🇺🇸Columbus, Ohio, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Rheumatology Associates
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute; Rheumatology
🇺🇸Boston, Massachusetts, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Houston Inst. For Clinical Research
🇺🇸Houston, Texas, United States
Univ of Calif, San Francisco; Rheumatology
🇺🇸San Francisco, California, United States
Eden Medical Center San Leandro Hospital
🇺🇸San Leandro, California, United States
Duke Medical Center
🇺🇸Durham, North Carolina, United States
Bone and Joint Hospital at St. Anthony Research Department
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
Rheumatology Assoc of North AL
🇺🇸Huntsville, Alabama, United States
Stanford University Med Ctr;Div of Immunology/Rheumatology
🇺🇸Palo Alto, California, United States
Intermountain Research Center
🇺🇸Boise, Idaho, United States
LA State Univ; Medicine
🇺🇸Shreveport, Louisiana, United States
Center For Rheumatology & Bone Research
🇺🇸Wheaton, Maryland, United States
NS-LIJ Health Systems; Rheum-Allergy Clin Immu
🇺🇸Lake Success, New York, United States
Seattle Rheumatology Assoc; Swedish Rheumatology Research
🇺🇸Seattle, Washington, United States
Coeur D'Alene Arthritis Clinic
🇺🇸Coeur d'Alene, Idaho, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum
🇺🇸Kansas City, Kansas, United States
Arthritis Northwest, Spokane
🇺🇸Spokane, Washington, United States
Michigan Arthritis Rsrch Ctr
🇺🇸Brighton, Michigan, United States
Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
Arthritis Associates PLLC
🇺🇸Chattanooga, Tennessee, United States
Physicians East Pa
🇺🇸Greenville, North Carolina, United States
Altoona Arthritis & Osteo Center
🇺🇸Duncansville, Pennsylvania, United States
Univ of Alabama School of Med; Clinical Immun Rheumatology
🇺🇸Birmingham, Alabama, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
University Of Michigan
🇺🇸Ann Arbor, Michigan, United States
Medical Univ of South Carolina
🇺🇸Charleston, South Carolina, United States
Kentuckiana Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services
🇺🇸Chapel Hill, North Carolina, United States
Portland Medical Associates
🇺🇸Portland, Oregon, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States