This study is no longer recruiting patients.

Sponsored by: Genentech Information provided by: Genentech ClinicalTrials.gov Identifier: NCT00087529

Purpose

This is a Phase II/III, randomized, double-blind, parallel group, placebo controlled, multicenter study to evaluate the safety and efficacy of rituximab in adults with PPMS.

Condition	Intervention	Phase
Multiple Sclerosis	Drug: Rituximab	Phase II Phase III

MedlinePlus related topics: Multiple Sclerosis

Study Type: Interventional
Study Design: Treatment

Official Title: A Phase II/III, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis

Further study details as provided by Genentech:

Primary Outcomes: To assess the efficacy of rituximab relative to placebo, as measured by the time to confirmed disease progression over a 96-week treatment period and to evaluate the safety and tolerability of rituximab in subjects with PPMS.
Secondary Outcomes: To evaluate the efficacy of rituximab compared with placebo.
Expected Total Enrollment: 435

Study start: June 2004

Eligibility

Ages Eligible for Study: 18 Years - 65 Years, Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

• Ability and willingness to provide written informed consent and to comply with the schedule of protocol assessments
• Age 18-65 years
• Definitive diagnosis of PPMS
• Disease duration of >=1 year
• EDSS at baseline between 2.0 and 6.5 points, inclusive
• Score of >=2.0 on the Functional Systems (FS) scale for the pyramidal system or gait that is due to lower extremity findings
• Presence of at least one of the following in a CSF specimen obtained during the screening period and analyzed by the central laboratory or results from a CSF sample obtained during the previous 24 months: IgG oligoclonal bands or Elevated CSF IgG index
• For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) during study treatment and for 1 year following the last dose of study drug

Exclusion Criteria:

• Pregnancy or lactation
• Incompatibility with MRI
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including atypical mycobacterial disease, but excluding fungal infections of nail beds or recurrent herpes zoster or simplex infections) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 30 days prior to screening or oral antibiotics within 14 days prior to screening
• History or presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis)
• History of cancer, including solid tumors and hematologic malignancies (except resected and fully resolved cutaneous basal cell and squamous cell carcinomas)
• History of alcohol or drug abuse within 6 months prior to screening
• History of or currently active primary or secondary immunodeficiency
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
• Presence of other significant, uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease that might interfere with a subject's ability to participate and to complete approximately 2.5 years of study participation
• History or presence of MS relapse or exacerbation
• History or presence of vascular disease potentially affecting the brain or spinal cord (e.g., stroke, transient ischemic attack, carotid stenosis, aortic aneurysm, intracranial aneurysm, hemorrhage, arteriovenous malformation)
• History or presence of myelopathy due to spinal cord compression by disk or vertebral disease
• History of severe, clinically significant central nervous system trauma (e.g., cerebral contusion, spinal cord compression)
• History of intracranial or intraspinal tumor (e.g., meningioma, glioma)
• History or presence of potential metabolic cause of myelopathy or encephalopathy (e.g., vitamin B12 deficiency, thyroid abnormalities)
• History or presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-cell lymphotropic virus type 1 [HTLV-1], or herpes zoster myelopathy)
• History of genetically inherited progressive CNS degenerative disorder (e.g., X-linked adrenoleukodystrophy, hereditary spastic paraparesis)
• Neuromyelitis optica
• History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren syndrome, Behcet disease)
• History or presence of sarcoidosis
• Previous treatment with rituximab (MabThera(R)/Rituxan(R))
• Previous treatment with lymphocyte-depleting therapies (e.g., cyclophosphamide, Campath(R), anti-CD4, cladribine, total body irradiation, bone marrow transplantation), except mitoxantrone, which should not be used 12 months prior to randomization
• Treatment with an investigational agent within 90 days or 5 half-lives of the investigational drug (whichever is longer) prior to randomization
• Receipt of a live vaccine within 30 days prior to randomization
• Systemic corticosteroid therapy within 30 days prior to randomization
• Treatment with IFN-Beta, glatiramer acetate, IVIG, or plasmapheresis within 60 days prior to randomization
• Treatment with non-lymphocyte-depleting immunosuppressive therapies (e.g., azathioprine, mycophenolate mofetil [MMF], cyclosporine) within 90 days prior to randomization
• Statins or hormone replacement therapy started within 30 days prior to randomization
• Vitamin B12 level below the lower limit of normal
• Positive rapid plasma reagin
• Serum creatinine >1.4 mg/dL for women or >1.6 mg/dL for men
• Aspartate aminotransferase or alanine aminotransferase >2.5 x the upper limit of normal
• Platelet count <100,000/ul
• Hemoglobin <8.5>
• Neutrophils <1.5>
• Lymphocyte count <0.1>
• B-cell count <1.1%>
• Serum IgG <5.65>
• Findings on brain or cervical spinal cord MRI consistent with conditions other than MS
• Electrocardiogram (ECG) showing a significant cardiac abnormality that the principal investigator determines may jeopardize the subject's health by participation in this study

Location Information

Arizona
Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, Phoenix, Arizona, 85013, United States
Mayo Clinic Scottsdale, Scottsdale, Arizona, 85259, United States
California
East Bay Region Associates in Neurology, Berkeley, California, 94705, United States
Neurological Research Institute Of East Bay, Walnut Creek, California, 94596, United States
USC Keck School of Medicine, Los Angeles, California, 90033, United States
Florida
Axiom Clinical Research of Florida, Tampa, Florida, 33609, United States
Neurology Associates, P.A., Maitland, Florida, 32751, United States
Neurological Services Of Orlando, Orlando, Florida, 32806, United States
Georgia
MS Center Of Atlanta, Atlanta, Georgia, 30327, United States
Shepherd Center, Atlanta, Georgia, 30309, United States
Illinois
University Of Chicago, Chicago, Illinois, 60637, United States
Indiana
Indiana University Medical Center, Indianapolis, Indiana, 46202, United States
Iowa
Mercy Medical Center, Des Moines, Iowa, 50314, United States
Kansas
University Of Kansas Medical Center, Kansas City, Kansas, 66160, United States
Maryland
Johns Hopkins Hospital, Baltimore, Maryland, 21287, United States
Massachusetts
Neurocare, Inc., Newton, Massachusetts, 02459, United States
Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States
University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, 01655, United States
Michigan
Henry Ford Hospital, Detroit, Michigan, 48202, United States
Michigan Institute For Neurological Disorders, Farmington Hills, Michigan, 48334, United States
Missouri
Washington University School of Medicine, St. Louis, Missouri, 63110, United States
New Hampshire
Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, 03756, United States
New Jersey
Gimbel MS Center, Teaneck, New Jersey, 07666, United States
New York
Albany Medical Center, Albany, New York, 12208, United States
SUNY Upstate Medical University, Syracuse, New York, 13202, United States
Mount Sinai Medical Center-CGD MS Center, New York, New York, 10029, United States
University Of Rochester, Rochester, New York, 14642, United States
North Carolina
Raleigh Neurology Associates, Raleigh, North Carolina, 27607, United States
MS Center-Carolinas Medical Center, Charlotte, North Carolina, 28207, United States
Ohio
The Ohio State University, Columbus, Ohio, 43221, United States
Oregon
Oregon Health and Science University, Portland, Oregon, 97239, United States
Pennsylvania
University Of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, United States
Geisinger Medical Center, Danville, Pennsylvania, 17822, United States
Rhode Island
Neurology Foundation INC/ Rhode Island Hospitals, Providence, Rhode Island, 02905, United States
Tennessee
Vanderbilt/Stallworth Rehab Hospital, Nashville, Tennessee, 37212, United States
Texas
University of Texas, Houston, Texas, 77030, United States
Neurology Clinic of San Antonio, San Antonio, Texas, 78201, United States
Maxine Mesinger MS Clinic/ Baylor College of Medicine, Houston, Texas, 77030, United States
University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States
Vermont
University Of Vermont, Burlington, Vermont, 05401, United States
Virginia
University Of Virginia, Charlottesville, Virginia, 22903, United States
Neurological Associates, Inc., Richmond, Virginia, 23230, United States
Washington
Holy Family MS Center, Spokane, Washington, 99208, United States
Virginia Mason Medical Center, Seattle, Washington, 98101, United States
Wisconsin
St. Luke's Medical Center/Center for Neurological Disorders, Milwaukee, Wisconsin, 53215, United States
Canada, Alberta
Foothills Medical Clinic, Calgary, Alberta, T2N 2T9, Canada
Canada, British Columbia
University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada
Canada, Nova Scotia
Dalhousie MS Research Unit, Halifax, Nova Scotia, B3H 1V7, Canada
Canada, Ontario
Ottawa Hospital, General Campus, Ottawa, Ontario, K1H 8L6, Canada
St. Michael's Hospital, Toronto, Ontario, M5B-1W8, Canada
Canada, Quebec
Hopital Charles LeMoyne, Greenfield Park, Quebec, J4V 2H1, Canada
Montreal Neurological Institute, Montreal, Quebec, H3A 2B4, Canada

Study chairs or principal investigators

Craig Smith, M.D., Study Director, Genentech

More Information

Study ID Numbers: U2786g
Last Updated: January 26, 2006
Record first received: July 9, 2004
ClinicalTrials.gov Identifier: NCT00087529
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-09-15

http://clinicaltrials.gov/ct/show/NCT00087529?order=2