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

Multiple Sclerosis Clinical Trial

Official title:

A Phase II, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab (Mabthera/Rituxan) in Adults With Relapsing Remitting Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00097188
• Other study ID #: U2787g
• Status: Completed
• Phase: Phase 2
• First received: November 18, 2004
• Last updated: February 28, 2014
• Start date: December 2004
• Est. completion date: December 2006

Study information

• Verified date: February 2014
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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?s 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

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• rituximab

Locations

Country	Name	City	State
United States	Neurology and Neuroscience Assoc.,INC	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	MS Center Of Atlanta	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	University of Maryland Hospital MS Center	Baltimore	Maryland
United States	Deaconess Billings Clinical Research Division	Billings	Montana
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Neurology Specialists of Dallas, PA	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Meritcare Neuroscience Clinic	Fargo	North Dakota
United States	Michigan Institute For Neurological Disorders	Farmington Hills	Michigan
United States	Maxine Mesinger MS Clinic/ Baylor College of Medicine	Houston	Texas
United States	University Of Kansas Medical Center	Kansas City	Kansas
United States	Loma Linda University	Loma Linda	California
United States	Kentucky Neuroscience Research	Louisville	Kentucky
United States	Neurology Associates, P.A.	Maitland	Florida
United States	Multiple Sclerosis Center of Brevard	Melbourne	Florida
United States	St. Luke's Medical Center/Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Sutter Gould Medical Foundation	Modesto	California
United States	Neurological Services Of Orlando	Orlando	Florida
United States	University Of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Phoenix Neurological Associates	Phoenix	Arizona
United States	Neurological Associates	Pompano Beach	Florida
United States	University Of California At Davis	Sacramento	California
United States	Neurology Clinic of San Antonio	San Antonio	Texas
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Holy Family MS Center	Spokane	Washington
United States	Neurology and Neurosurgery Associates of Tacoma, Inc., P.S.	Tacoma	Washington
United States	MS Center of Vero Beach	Vero Beach	Florida
United States	Neurological Research Institute Of East Bay	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7 — View Citation

Smith CH, Waubant E, Langer-Gould A. Absence of neuromyelitis optica IgG antibody in an active relapsing-remitting multiple sclerosis population. J Neuroophthalmol. 2009 Jun;29(2):104-6. doi: 10.1097/WNO.0b013e3181a63606. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To evaluate the efficacy of rituximab compared with placebo.