A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus

Lupus Erythematosus, Systemic Clinical Trial

— EXPLORER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00137969
• Other study ID #: U2971g
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 10, 2005
• Est. completion date: August 25, 2008

Study information

• Verified date: June 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 262
• Est. completion date: August 25, 2008
• Est. primary completion date: August 25, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Drug:
• Rituximab
Rituximab will be supplied as a sterile liquid for IV administration.
• Placebo
Placebo will be supplied as a sterile liquid for IV administration.
• Prednisone

• Acetaminophen

• Diphenhydramine

Locations

Country	Name	City	State
Canada	St. Joseph'S Health Care Centre	London	Ontario
Canada	Univ of Manitoba, Health Scien; Arthritis Centre	Winnipeg	Manitoba
United States	Center for Rheumatology, State Uni. of New York	Albany	New York
United States	University Of Michigan	Ann Arbor	Michigan
United States	Emory Uni ; Division of Rheumatology	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Arthritis & Rheumatism; Disease Specialities	Aventura	Florida
United States	Johns Hopkins Uni	Baltimore	Maryland
United States	East Penn Rheumatology Associates, Pc	Bethlehem	Pennsylvania
United States	Univ of Alabama School of Med; Clinical Immun Rheumatology	Birmingham	Alabama
United States	Intermountain Research Center	Boise	Idaho
United States	Dana-Farber Cancer Institute; Rheumatology	Boston	Massachusetts
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Michigan Arthritis Rsrch Ctr	Brighton	Michigan
United States	SUNY Downstate Medical Center.	Brooklyn	New York
United States	University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services	Chapel Hill	North Carolina
United States	Medical Univ of South Carolina	Charleston	South Carolina
United States	University of Virginia Med Ctr; Div of Ped Respiratory Med	Charlottesville	Virginia
United States	Arthritis Associates PLLC	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	Rheumatology Associates	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Coeur D'Alene Arthritis Clinic	Coeur d'Alene	Idaho
United States	Ohio State University; Division of Nephrology	Columbus	Ohio
United States	Arthritis Centers of Texas	Dallas	Texas
United States	Metroplex Clinical Research	Dallas	Texas
United States	Altoona Arthritis & Osteo Center	Duncansville	Pennsylvania
United States	Duke Medical Center	Durham	North Carolina
United States	Tri-State Arth & Rheum Center	Evansville	Indiana
United States	Physicians East Pa	Greenville	North Carolina
United States	Houston Inst. For Clinical Research	Houston	Texas
United States	Rheumatology Assoc of North AL	Huntsville	Alabama
United States	Family Arthritis Center	Jupiter	Florida
United States	Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum	Kansas City	Kansas
United States	Univ of California, San Diego	La Jolla	California
United States	NS-LIJ Health Systems; Rheum-Allergy Clin Immu	Lake Success	New York
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Univ of Calif., Los Angeles; Rheumatology	Los Angeles	California
United States	Kentuckiana Cancer Institute	Louisville	Kentucky
United States	Arthritis & Osteoporosis Associates, LLP	Lubbock	Texas
United States	Feinstein Institute for Medical Research	Manhasset	New York
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	Bone and Joint Hospital at St. Anthony Research Department	Oklahoma City	Oklahoma
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Buffalo Rheumatology Associates	Orchard Park	New York
United States	Stanford University Med Ctr;Div of Immunology/Rheumatology	Palo Alto	California
United States	Arizona Arthritis & Rheumatology Research, Pllc	Paradise Valley	Arizona
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Uni of Pennslyvania Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Long Island Osteo/Arth Center	Plainview	New York
United States	Portland Medical Associates	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester - Strong Memorial Hospital	Rochester	New York
United States	Washington University; Rheumatology Division	Saint Louis	Missouri
United States	Univ of Calif, San Francisco; Rheumatology	San Francisco	California
United States	Eden Medical Center San Leandro Hospital	San Leandro	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Seattle Rheumatology Assoc; Swedish Rheumatology Research	Seattle	Washington
United States	LA State Univ; Medicine	Shreveport	Louisiana
United States	Arthritis Northwest, Spokane	Spokane	Washington
United States	Texas Research Center	Sugar Land	Texas
United States	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma
United States	Center For Rheumatology & Bone Research	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period	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	From baseline to 52 weeks
Secondary	Number of Participants Who Achieved an MCR (Excluding PCR)	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.	From baseline to 52 weeks
Secondary	Number of Participants Who Achieved a PCR (Including MCR)	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.	From baseline to 52 Weeks
Secondary	Number of Participants Who Achieved a BILAG C or Better in All Domains	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.	24 weeks
Secondary	Time to First Moderate or Severe Flare	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.	52 weeks
Secondary	Change in SLE Expanded Health Survey Physical Function Score From Baseline	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.	From baseline to 52 weeks
Secondary	Number of Participants Who Achieved an MCR in The ITT Population	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.	From Weeks 24 to 52