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

NCT ID: NCT00137969

Last Updated: 2019-08-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

262 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-05-10

Study Completion Date

2008-08-25

Brief Summary

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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

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Conditions

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Lupus Erythematosus, Systemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Rituximab 1000 mg + 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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Rituximab will be supplied as a sterile liquid for IV administration.

Prednisone

Intervention Type DRUG

Acetaminophen

Intervention Type DRUG

Diphenhydramine

Intervention Type DRUG

Placebo + 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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be supplied as a sterile liquid for IV administration.

Prednisone

Intervention Type DRUG

Acetaminophen

Intervention Type DRUG

Diphenhydramine

Intervention Type DRUG

Interventions

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Rituximab

Rituximab will be supplied as a sterile liquid for IV administration.

Intervention Type DRUG

Placebo

Placebo will be supplied as a sterile liquid for IV administration.

Intervention Type DRUG

Prednisone

Intervention Type DRUG

Acetaminophen

Intervention Type DRUG

Diphenhydramine

Intervention Type DRUG

Other Intervention Names

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Rituxan MabThera Zytux

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Brunetta, M.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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Univ of Alabama School of Med; Clinical Immun Rheumatology

Birmingham, Alabama, United States

Site Status

Rheumatology Assoc of North AL

Huntsville, Alabama, United States

Site Status

Arizona Arthritis & Rheumatology Research, Pllc

Paradise Valley, Arizona, United States

Site Status

Univ of California, San Diego

La Jolla, California, United States

Site Status

Univ of Calif., Los Angeles; Rheumatology

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Stanford University Med Ctr;Div of Immunology/Rheumatology

Palo Alto, California, United States

Site Status

Univ of Calif, San Francisco; Rheumatology

San Francisco, California, United States

Site Status

Eden Medical Center San Leandro Hospital

San Leandro, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Arthritis & Rheumatism; Disease Specialities

Aventura, Florida, United States

Site Status

Family Arthritis Center

Jupiter, Florida, United States

Site Status

Emory Uni ; Division of Rheumatology

Atlanta, Georgia, United States

Site Status

Intermountain Research Center

Boise, Idaho, United States

Site Status

Coeur D'Alene Arthritis Clinic

Coeur d'Alene, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rheumatology Associates

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Tri-State Arth & Rheum Center

Evansville, Indiana, United States

Site Status

Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum

Kansas City, Kansas, United States

Site Status

Kentuckiana Cancer Institute

Louisville, Kentucky, United States

Site Status

LA State Univ; Medicine

Shreveport, Louisiana, United States

Site Status

Johns Hopkins Uni

Baltimore, Maryland, United States

Site Status

Center For Rheumatology & Bone Research

Wheaton, Maryland, United States

Site Status

Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute; Rheumatology

Boston, Massachusetts, United States

Site Status

University Of Michigan

Ann Arbor, Michigan, United States

Site Status

Michigan Arthritis Rsrch Ctr

Brighton, Michigan, United States

Site Status

Washington University; Rheumatology Division

St Louis, Missouri, United States

Site Status

Center for Rheumatology, State Uni. of New York

Albany, New York, United States

Site Status

SUNY Downstate Medical Center.

Brooklyn, New York, United States

Site Status

NS-LIJ Health Systems; Rheum-Allergy Clin Immu

Lake Success, New York, United States

Site Status

Feinstein Institute for Medical Research

Manhasset, New York, United States

Site Status

NYU-Hosp for Joint Diseases; Rheum and Med

New York, New York, United States

Site Status

Hospital for Special Surgery

New York, New York, United States

Site Status

Buffalo Rheumatology Associates

Orchard Park, New York, United States

Site Status

Long Island Osteo/Arth Center

Plainview, New York, United States

Site Status

University of Rochester - Strong Memorial Hospital

Rochester, New York, United States

Site Status

University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services

Chapel Hill, North Carolina, United States

Site Status

Duke Medical Center

Durham, North Carolina, United States

Site Status

Physicians East Pa

Greenville, North Carolina, United States

Site Status

Ohio State University; Division of Nephrology

Columbus, Ohio, United States

Site Status

Bone and Joint Hospital at St. Anthony Research Department

Oklahoma City, Oklahoma, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Oklahoma Center For Arthritis Therapy & Research

Tulsa, Oklahoma, United States

Site Status

Portland Medical Associates

Portland, Oregon, United States

Site Status

East Penn Rheumatology Associates, Pc

Bethlehem, Pennsylvania, United States

Site Status

Altoona Arthritis & Osteo Center

Duncansville, Pennsylvania, United States

Site Status

Uni of Pennslyvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical Univ of South Carolina

Charleston, South Carolina, United States

Site Status

Arthritis Associates PLLC

Chattanooga, Tennessee, United States

Site Status

Metroplex Clinical Research

Dallas, Texas, United States

Site Status

Arthritis Centers of Texas

Dallas, Texas, United States

Site Status

Houston Inst. For Clinical Research

Houston, Texas, United States

Site Status

Arthritis & Osteoporosis Associates, LLP

Lubbock, Texas, United States

Site Status

Texas Research Center

Sugar Land, Texas, United States

Site Status

University of Virginia Med Ctr; Div of Ped Respiratory Med

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Seattle Rheumatology Assoc; Swedish Rheumatology Research

Seattle, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Arthritis Northwest, Spokane

Spokane, Washington, United States

Site Status

Univ of Manitoba, Health Scien; Arthritis Centre

Winnipeg, Manitoba, Canada

Site Status

St. Joseph'S Health Care Centre

London, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 20039413 (View on PubMed)

Other Identifiers

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U2971g

Identifier Type: -

Identifier Source: org_study_id

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