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A Study to Evaluate Rituximab in Adults With Relapsing Remitting Multiple Sclerosis

Phase 2
Completed
Conditions
Multiple Sclerosis
Registration Number
NCT00097188
Lead Sponsor
Genentech, Inc.
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
104
Inclusion Criteria
  • Ability and willingness to provide written informed consent and to comply with the schedule of protocol assessments
  • Age 18--55 years, inclusive
  • Diagnosis of relapsing MS, as defined by McDonald Criteria 1--4
  • History of at least one relapse in the subject's medical records during the 1 year prior to randomization
  • EDSS at screening between 0 and 5.0 points, inclusive
  • For subjects of reproductive potential (males and females), ability and willingness to use a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) during the study, including the safety follow-up period, and for up to 1 year after their last dose of study drug, even if they have discontinued early from the study
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, or mycobacterial infection, or other infection (including atypical mycobacterial disease, but excluding fungal infections of nail beds or recurrent herpes 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, or syphilis)
  • History of cancer, including solid tumors and hematologic malignancies (except fully resolved and resected cutaneous basal cell and squamous cell carcinomas of the skin)
  • History of alcohol or drug abuse within 6 months prior to screening
  • History of or currently active primary or secondary immunodeficiency
  • Presence of significant, uncontrolled disease of the cardiovascular, pulmonary, renal, hepatic, endocrine, or gastrointestinal systems
  • Diagnosis of secondary progressive, primary progressive, or progressive relapsing MS
  • History or presence of vascular disease potentially affecting brain or spinal cord (e.g., stroke, transient ischemic attack, severe 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 CNS 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 encephalopathy or myelopathy (e.g., untreated vitamin B12 deficiency, untreated thyroid deficiency)
  • History or presence of infectious causes of encephalopathy or myelopathy (e.g., syphilis, Lyme disease, human T-cell lymphotropic virus type 1 [HTLV-1], herpes zoster myelopathy)
  • Neuromyelitis optica
  • History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, antiphospholipid antibody syndrome, Sjogren๏ฟฝs syndrome, Behcet disease)
  • History or presence of sarcoidosis
  • Relapse within 30 days prior to randomization
  • Previous treatment with rituximab (MabThera(R)/Rituxan(R))
  • Treatment with any investigational agent within 90 days of randomization or five half-lives of the investigational drug (whichever is longer)
  • Receipt of a live vaccine within 30 days prior to randomization
  • Previous treatment with lymphocyte-depleting therapies (e.g., Campath(R), anti-CD4, cladribine, total body irradiation, bone marrow transplantation)
  • Treatment with cyclophosphamide or mitoxantrone within 12 months of randomization
  • Systemic corticosteroid therapy within 30 days of randomization
  • Treatment with IFN-Beta; or Copaxone(R) within 60 days of randomization
  • Treatment with IVIG within 60 days of randomization
  • Plasmapheresis within 60 days of randomization
  • Treatment with non-lymphocyte depleting immunosuppressive therapies (e.g., azathioprine, mycophenolate mofetil, cyclosporine) within 90 days prior to randomization
  • Statins or hormone replacement therapy started within 30 days of randomization
  • Positive pregnancy test
  • B-cell count <1.1% (reported as percent CD19)
  • Vitamin B12 below the lower limit of normal with an abnormal methylmalonic acid level
  • Positive rapid plasma reagin
  • Serum creatinine >1.4 mg/dL for women or >1.6 mg/dL for men
  • Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >2.5 x the upper limit of normal
  • Platelet count <100,000/mL
  • Hemoglobin <8.5 g/dL
  • Neutrophils <1.5 x 10^3/mL
  • Serum IgG levels below 5.65 mg/mL and serum IgM levels below 0.55 mg/mL
  • Findings on brain MRI scan consistent with clinically significant conditions other than MS
  • Electrocardiogram (ECG) showing significant abnormality that the treating investigator determines may jeopardize the subject's health (i.e., acute ischemia, left bundle branch, or bifascicular block)

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To investigate the efficacy of rituximab compared with placebo, as measured by MRI scans of the brain for the total number of lesions observed, and to evaluate the safety and tolerability of rituximab in subjects with RRMS.
Secondary Outcome Measures
NameTimeMethod
To evaluate the efficacy of rituximab compared with placebo.

Trial Locations

Locations (31)

Michigan Institute For Neurological Disorders

๐Ÿ‡บ๐Ÿ‡ธ

Farmington Hills, Michigan, United States

Neurology and Neuroscience Assoc.,INC

๐Ÿ‡บ๐Ÿ‡ธ

Akron, Ohio, United States

MS Center of Vero Beach

๐Ÿ‡บ๐Ÿ‡ธ

Vero Beach, Florida, United States

Multiple Sclerosis Center of Brevard

๐Ÿ‡บ๐Ÿ‡ธ

Melbourne, Florida, United States

Geisinger Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Danville, Pennsylvania, United States

Sutter Gould Medical Foundation

๐Ÿ‡บ๐Ÿ‡ธ

Modesto, California, United States

Neurology Associates, P.A.

๐Ÿ‡บ๐Ÿ‡ธ

Maitland, Florida, United States

Loma Linda University

๐Ÿ‡บ๐Ÿ‡ธ

Loma Linda, California, United States

University Of California At Davis

๐Ÿ‡บ๐Ÿ‡ธ

Sacramento, California, United States

Albany Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Albany, New York, United States

University Of Pennsylvania Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Philadelphia, Pennsylvania, United States

Medical College of Georgia

๐Ÿ‡บ๐Ÿ‡ธ

Augusta, Georgia, United States

Kentucky Neuroscience Research

๐Ÿ‡บ๐Ÿ‡ธ

Louisville, Kentucky, United States

Neurology Clinic of San Antonio

๐Ÿ‡บ๐Ÿ‡ธ

San Antonio, Texas, United States

Virginia Mason Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Seattle, Washington, United States

Neurological Associates

๐Ÿ‡บ๐Ÿ‡ธ

Pompano Beach, Florida, United States

The Ohio State University

๐Ÿ‡บ๐Ÿ‡ธ

Columbus, Ohio, United States

The Cleveland Clinic Foundation

๐Ÿ‡บ๐Ÿ‡ธ

Cleveland, Ohio, United States

Neurology Specialists of Dallas, PA

๐Ÿ‡บ๐Ÿ‡ธ

Dallas, Texas, United States

Maxine Mesinger MS Clinic/ Baylor College of Medicine

๐Ÿ‡บ๐Ÿ‡ธ

Houston, Texas, United States

Neurological Research Institute Of East Bay

๐Ÿ‡บ๐Ÿ‡ธ

Walnut Creek, California, United States

Neurological Services Of Orlando

๐Ÿ‡บ๐Ÿ‡ธ

Orlando, Florida, United States

MS Center Of Atlanta

๐Ÿ‡บ๐Ÿ‡ธ

Atlanta, Georgia, United States

University of Maryland Hospital MS Center

๐Ÿ‡บ๐Ÿ‡ธ

Baltimore, Maryland, United States

Holy Family MS Center

๐Ÿ‡บ๐Ÿ‡ธ

Spokane, Washington, United States

Neurology and Neurosurgery Associates of Tacoma, Inc., P.S.

๐Ÿ‡บ๐Ÿ‡ธ

Tacoma, Washington, United States

St. Luke's Medical Center/Center for Neurological Disorders

๐Ÿ‡บ๐Ÿ‡ธ

Milwaukee, Wisconsin, United States

Phoenix Neurological Associates

๐Ÿ‡บ๐Ÿ‡ธ

Phoenix, Arizona, United States

Deaconess Billings Clinical Research Division

๐Ÿ‡บ๐Ÿ‡ธ

Billings, Montana, United States

Meritcare Neuroscience Clinic

๐Ÿ‡บ๐Ÿ‡ธ

Fargo, North Dakota, United States

University Of Kansas Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Kansas City, Kansas, United States

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