Clinical trial NCT00137969: A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Lupus Erythematosus, Systemic
Keywords: Rituxan
SLE
Lupus
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2005-08-30
Enrollment: 262
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: From baseline to 52 weeks
Secondary outcomes:
measure: Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period
timeFrame: From baseline to 52 weeks
measure: Number of Participants Who Achieved an MCR (Excluding PCR)
timeFrame: From baseline to 52 weeks
measure: Number of Participants Who Achieved a PCR (Including MCR)
timeFrame: From baseline to 52 Weeks
measure: Number of Participants Who Achieved a BILAG C or Better in All Domains
timeFrame: 24 weeks
measure: Time to First Moderate or Severe Flare
timeFrame: 52 weeks
measure: Change in SLE Expanded Health Survey Physical Function Score From Baseline
timeFrame: From baseline to 52 weeks
measure: Number of Participants Who Achieved an MCR in The ITT Population
timeFrame: From Weeks 24 to 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama School of Med; Clinical Immun Rheumatology
state: Alabama
city: Huntsville
country: United States
facility: Rheumatology Assoc of North AL
state: Alabama
city: Paradise Valley
country: United States
facility: Arizona Arthritis & Rheumatology Research, Pllc
state: Arizona
city: La Jolla
country: United States
facility: Univ of California, San Diego
state: California
city: Los Angeles
country: United States
facility: Univ of Calif., Los Angeles; Rheumatology
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Med Ctr;Div of Immunology/Rheumatology
state: California
city: San Francisco
country: United States
facility: Univ of Calif, San Francisco; Rheumatology
state: California
city: San Leandro
country: United States
facility: Eden Medical Center San Leandro Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Aventura
country: United States
facility: Arthritis & Rheumatism; Disease Specialities
state: Florida
city: Jupiter
country: United States
facility: Family Arthritis Center
state: Florida
city: Atlanta
country: United States
facility: Emory Uni ; Division of Rheumatology
state: Georgia
city: Boise
country: United States
facility: Intermountain Research Center
state: Idaho
city: Coeur d'Alene
country: United States
facility: Coeur D'Alene Arthritis Clinic
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rheumatology Associates
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Evansville
country: United States
facility: Tri-State Arth & Rheum Center
state: Indiana
city: Kansas City
country: United States
facility: Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute
state: Kentucky
city: Shreveport
country: United States
facility: LA State Univ; Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Uni
state: Maryland
city: Wheaton
country: United States
facility: Center For Rheumatology & Bone Research
state: Maryland
city: Boston
country: United States
facility: Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute; Rheumatology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Brighton
country: United States
facility: Michigan Arthritis Rsrch Ctr
state: Michigan
city: Saint Louis
country: United States
facility: Washington University; Rheumatology Division
state: Missouri
city: Albany
country: United States
facility: Center for Rheumatology, State Uni. of New York
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center.
state: New York
city: Lake Success
country: United States
facility: NS-LIJ Health Systems; Rheum-Allergy Clin Immu
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: NYU-Hosp for Joint Diseases; Rheum and Med
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Orchard Park
country: United States
facility: Buffalo Rheumatology Associates
state: New York
city: Plainview
country: United States
facility: Long Island Osteo/Arth Center
state: New York
city: Rochester
country: United States
facility: University of Rochester - Strong Memorial Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services
state: North Carolina
city: Durham
country: United States
facility: Duke Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Physicians East Pa
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University; Division of Nephrology
state: Ohio
city: Oklahoma City
country: United States
facility: Bone and Joint Hospital at St. Anthony Research Department
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Center For Arthritis Therapy & Research
state: Oklahoma
city: Portland
country: United States
facility: Portland Medical Associates
state: Oregon
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, Pc
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Arthritis & Osteo Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Uni of Pennslyvania Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Univ of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Arthritis Associates PLLC
state: Tennessee
city: Dallas
country: United States
facility: Metroplex Clinical Research
state: Texas
city: Dallas
country: United States
facility: Arthritis Centers of Texas
state: Texas
city: Houston
country: United States
facility: Houston Inst. For Clinical Research
state: Texas
city: Lubbock
country: United States
facility: Arthritis & Osteoporosis Associates, LLP
state: Texas
city: Sugar Land
country: United States
facility: Texas Research Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Med Ctr; Div of Ped Respiratory Med
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Rheumatology Assoc; Swedish Rheumatology Research
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest, Spokane
state: Washington
city: Winnipeg
country: Canada
facility: Univ of Manitoba, Health Scien; Arthritis Centre
state: Manitoba
city: London
country: Canada
facility: St. Joseph'S Health Care Centre
state: Ontario
Study officials:
affiliation: Genentech, Inc.
name: Paul Brunetta, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.