Clinical trial NCT00097188: A Study to Evaluate Rituximab in Adults With Relapsing Remitting Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Relapsing remitting multiple sclerosis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2004-11-19
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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 outcomes:
measure: To evaluate the efficacy of rituximab compared with placebo.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Modesto
country: United States
facility: Sutter Gould Medical Foundation
state: California
city: Sacramento
country: United States
facility: University Of California At Davis
state: California
city: Walnut Creek
country: United States
facility: Neurological Research Institute Of East Bay
state: California
city: Maitland
country: United States
facility: Neurology Associates, P.A.
state: Florida
city: Melbourne
country: United States
facility: Multiple Sclerosis Center of Brevard
state: Florida
city: Orlando
country: United States
facility: Neurological Services Of Orlando
state: Florida
city: Pompano Beach
country: United States
facility: Neurological Associates
state: Florida
city: Vero Beach
country: United States
facility: MS Center of Vero Beach
state: Florida
city: Atlanta
country: United States
facility: MS Center Of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Kansas City
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kentucky Neuroscience Research
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Hospital MS Center
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan Institute For Neurological Disorders
state: Michigan
city: Billings
country: United States
facility: Deaconess Billings Clinical Research Division
state: Montana
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Fargo
country: United States
facility: Meritcare Neuroscience Clinic
state: North Dakota
city: Akron
country: United States
facility: Neurology and Neuroscience Assoc.,INC
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University Of Pennsylvania Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Neurology Specialists of Dallas, PA
state: Texas
city: Houston
country: United States
facility: Maxine Mesinger MS Clinic/ Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Neurology Clinic of San Antonio
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Holy Family MS Center
state: Washington
city: Tacoma
country: United States
facility: Neurology and Neurosurgery Associates of Tacoma, Inc., P.S.
state: Washington
city: Milwaukee
country: United States
facility: St. Luke's Medical Center/Center for Neurological Disorders
state: Wisconsin
Study officials:
affiliation: Genentech, Inc.
name: Craig Smith, M.D.
role: STUDY_DIRECTOR
References:
citation: 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):676-88. doi: 10.1056/NEJMoa0706383.
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.