A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus
EXPLORER
Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II/III Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With Moderate to Severe Systemic Lupus Erythematosus
1 other identifier
interventional
262
2 countries
65
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2005
Typical duration for phase_2
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 10, 2005
CompletedFirst Submitted
Initial submission to the registry
August 26, 2005
CompletedFirst Posted
Study publicly available on registry
August 30, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 25, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 25, 2008
CompletedResults Posted
Study results publicly available
December 10, 2010
CompletedAugust 20, 2019
June 1, 2017
3.3 years
August 26, 2005
June 5, 2009
August 2, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
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.
From baseline to 52 weeks
Secondary Outcomes (7)
Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period
From baseline to 52 weeks
Number of Participants Who Achieved an MCR (Excluding PCR)
From baseline to 52 weeks
Number of Participants Who Achieved a PCR (Including MCR)
From baseline to 52 Weeks
Number of Participants Who Achieved a BILAG C or Better in All Domains
24 weeks
Time to First Moderate or Severe Flare
52 weeks
- +2 more secondary outcomes
Study Arms (2)
Rituximab 1000 mg + prednisone
EXPERIMENTALParticipants 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 COMPARATORParticipants 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.
Interventions
Rituximab will be supplied as a sterile liquid for IV administration.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (65)
Univ of Alabama School of Med; Clinical Immun Rheumatology
Birmingham, Alabama, 35294, United States
Rheumatology Assoc of North AL
Huntsville, Alabama, 35801, United States
Arizona Arthritis & Rheumatology Research, Pllc
Paradise Valley, Arizona, 85253, United States
Univ of California, San Diego
La Jolla, California, 92037, United States
Univ of Calif., Los Angeles; Rheumatology
Los Angeles, California, 90025, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Stanford University Med Ctr;Div of Immunology/Rheumatology
Palo Alto, California, 94304, United States
Univ of Calif, San Francisco; Rheumatology
San Francisco, California, 94143-0111, United States
Eden Medical Center San Leandro Hospital
San Leandro, California, 94578, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Arthritis & Rheumatism; Disease Specialities
Aventura, Florida, 33180, United States
Family Arthritis Center
Jupiter, Florida, 33458, United States
Emory Uni ; Division of Rheumatology
Atlanta, Georgia, 30303, United States
Intermountain Research Center
Boise, Idaho, 83702, United States
Coeur D'Alene Arthritis Clinic
Coeur d'Alene, Idaho, 83814, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rheumatology Associates
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Tri-State Arth & Rheum Center
Evansville, Indiana, 47714, United States
Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum
Kansas City, Kansas, 66160, United States
Kentuckiana Cancer Institute
Louisville, Kentucky, 40202, United States
LA State Univ; Medicine
Shreveport, Louisiana, 71103, United States
Johns Hopkins Uni
Baltimore, Maryland, 21205, United States
Center For Rheumatology & Bone Research
Wheaton, Maryland, 20902, United States
Tufts - New England Medical Center
Boston, Massachusetts, 02111, United States
Dana-Farber Cancer Institute; Rheumatology
Boston, Massachusetts, 02215-5501, United States
University Of Michigan
Ann Arbor, Michigan, 48109, United States
Michigan Arthritis Rsrch Ctr
Brighton, Michigan, 48116, United States
Washington University; Rheumatology Division
St Louis, Missouri, 63110, United States
Center for Rheumatology, State Uni. of New York
Albany, New York, 12206, United States
SUNY Downstate Medical Center.
Brooklyn, New York, 11203, United States
NS-LIJ Health Systems; Rheum-Allergy Clin Immu
Lake Success, New York, 11042, United States
Feinstein Institute for Medical Research
Manhasset, New York, 11030, United States
NYU-Hosp for Joint Diseases; Rheum and Med
New York, New York, 10003, United States
Hospital for Special Surgery
New York, New York, 10021, United States
Buffalo Rheumatology Associates
Orchard Park, New York, 14127, United States
Long Island Osteo/Arth Center
Plainview, New York, 11803, United States
University of Rochester - Strong Memorial Hospital
Rochester, New York, 14642, United States
University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services
Chapel Hill, North Carolina, 27514, United States
Duke Medical Center
Durham, North Carolina, 27710, United States
Physicians East Pa
Greenville, North Carolina, 27834, United States
Ohio State University; Division of Nephrology
Columbus, Ohio, 43210, United States
Bone and Joint Hospital at St. Anthony Research Department
Oklahoma City, Oklahoma, 73103, United States
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, 73104, United States
Oklahoma Center For Arthritis Therapy & Research
Tulsa, Oklahoma, 74104, United States
Portland Medical Associates
Portland, Oregon, 97224, United States
East Penn Rheumatology Associates, Pc
Bethlehem, Pennsylvania, 18015, United States
Altoona Arthritis & Osteo Center
Duncansville, Pennsylvania, 16635, United States
Uni of Pennslyvania Medical Center
Philadelphia, Pennsylvania, 19104, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Medical Univ of South Carolina
Charleston, South Carolina, 29425, United States
Arthritis Associates PLLC
Chattanooga, Tennessee, 37404, United States
Metroplex Clinical Research
Dallas, Texas, 75231, United States
Arthritis Centers of Texas
Dallas, Texas, 75246, United States
Houston Inst. For Clinical Research
Houston, Texas, 77074, United States
Arthritis & Osteoporosis Associates, LLP
Lubbock, Texas, 79424, United States
Texas Research Center
Sugar Land, Texas, 77479, United States
University of Virginia Med Ctr; Div of Ped Respiratory Med
Charlottesville, Virginia, 22908, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Seattle Rheumatology Assoc; Swedish Rheumatology Research
Seattle, Washington, 98104, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Arthritis Northwest, Spokane
Spokane, Washington, 99204, United States
Univ of Manitoba, Health Scien; Arthritis Centre
Winnipeg, Manitoba, R3A1M4, Canada
St. Joseph'S Health Care Centre
London, Ontario, N6A 4V2, Canada
Related Publications (1)
Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010 Jan;62(1):222-33. doi: 10.1002/art.27233.
PMID: 20039413DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffman-LaRoche
Study Officials
- STUDY DIRECTOR
Paul Brunetta, M.D.
Genentech, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2005
First Posted
August 30, 2005
Study Start
May 10, 2005
Primary Completion
August 25, 2008
Study Completion
August 25, 2008
Last Updated
August 20, 2019
Results First Posted
December 10, 2010
Record last verified: 2017-06