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Sponsors and Collaborators: |
University of California, San Francisco Genentech |
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Information provided by: | University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT00501748 |
The goal of this research study is to investigate whether Rituximab is safe to use in patients suffering from NMO, or who are at high risk for developing NMO. It is thought that NMO is caused by the immune system reacting against the optic nerves and spinal cord. B cells are a part of the immune system that may contribute to the illness. Rituximab is an antibody that depletes B cells. Depletion of these B cells with Rituximab may induce remission of the disease. Because pathological and serological studies suggest that NMO appears to be, at least in part, a B-cell mediated disease Rituximab, is an attractive candidate for this treatment
Condition | Intervention | Phase |
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Neuromyelitis Optica |
Drug: Rituximab |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Open Label Study of Safety and Tolerability of Rituximab in Neuromyelitis Optica, Recurrent Transverse Myelitis and Recurrent Bilateral Simultaneous Optic Neuritis |
Estimated Enrollment: | 20 |
Study Start Date: | January 2004 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
Rituximab is a genetically engineered, chimeric, murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant pre-B and mature B cells. The antibody is an IgG1 immunoglobulin containing murine light- and heavy chain variable region sequences and human constant region sequences. Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids (based on cDNA analysis) and has an approximate molecular mass of 145 kD. Rituximab has a binding affinity for the CD20 antigen of ~8.0 nM.
Rituximab was developed by Biogen Idec and Genentech, Inc. It was approved by the FDA in 1997 for the treatment of relapsed or refractory low grade or follicular, CD20+, B-cell non-Hodgkin's lymphoma (NHL).
Rituximab has also been studied in a variety of non-malignant autoimmune disorders where B cells and auto antibodies appear to play a role in pathophysiology. Rituximab has been reported to relieve signs and symptoms of rheumatoid arthritis , lupus , immune thrombocytopenia , autoimmune anemia , autoimmune neuropathy , and paraneoplastic opsoclonus/myoclonus .
A Phase II study (WA16291) has been completed in patients with rheumatoid arthritis (RA) . A total of 161 patients were randomized to 4 treatment arms: Methotrexate, Rituximab alone, Rituximab and Methotrexate, Rituximab and Cyclophosphamide. Two doses of Rituximab, 1 gm each, were administered IV two weeks apart. Infusion reactions were observed in 36% of patients during their first infusion of Rituximab compared to 30% for placebo . Four Rituximab-treated patients developed serious infections, for a rate of 4.6 per 100 patient years. For context, the rate of infections requiring hospital admission was 9.57 per 100 patient years in a community based epidemiologic study in RA. (Doran et al. 2002).
We treated 8 patients with NMO with Rituximab and observed that Rituximab appears to be well tolerated with 0/8 of the patients suffering serious adverse reactions that could be directly related to Rituximab administration. Moreover, 7/8 patients experienced decrease in neurological disability following treatment, suggesting that B-cell depletion may enhance neurological recovery from attacks. 7/8 of the patients remained attack-free within a period of 18 months of follow-up on average (range 3 to 12 months) following treatment. We observed one attack following treatment in a single patient, whereas 14 attacks would have been predicted by the pre-treatment attack rate (p=0.012, paired t test comparing pre- and post-treatment attack rates). Nevertheless, the observed impact of treatment on recovery is more than what would be expected from spontaneous recovery and deserves further investigation. If B cells are essential for pathogenesis of recurrent attacks in NMO, B cell depletion may induce sustained remission. We also observed in one case, a dramatic recovery of electrophysiological conduction in the optic nerves (visual evoked potentials), which implies that in this case, rituxan did not impair repair mechanisms, for example, demyelination following the acute attack.
Ages Eligible for Study: | 12 Years to 86 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion criteria
Criteria for neuromyelitis optica:
Criteria for high risk for neuromyelitis optica:
recurrent bilateral simultaneous optic neuritis with at least 3 months time between each attack.
In addition patients should have one major supportive criteria OR two minor supportive criteria:
Minor supportive criteria:
Exclusion Criteria:
United States, California | |
UCSF MS Center , 350 Parnassus Ave , suite #908 | |
San Francisco, California, United States, 94117 | |
UCSF MS Center , 350 Parnassus Ave , suite #908 | |
San Francisco, California, United States, 94117 | |
United States, New York | |
The Neurological Institute of New York MS Center | |
Columbia University Medical Center 710 West 168th Street,, New York, United States, 10032 |
Principal Investigator: | Bruce Cree, MD, PhD | MS Center , UCSF |
Responsible Party: | Genentech ( UCSF MS Center ) |
Study ID Numbers: | H7620-25392-04 |
Study First Received: | July 12, 2007 |
Last Updated: | October 9, 2008 |
ClinicalTrials.gov Identifier: | NCT00501748 |
Health Authority: | United States: Institutional Review Board |
Neuromyelitis Optica acute transverse myelitis |
Papillitis Spinal Cord Diseases Neuromyelitis Optica Demyelinating diseases Neurodegenerative Diseases Neuritis Multiple Sclerosis Myelitis, Transverse Autoimmune Diseases of the Nervous System Nervous System Neoplasms Immunoglobulins Optic Neuritis Autoimmune Diseases Devic disease |
Demyelinating Diseases Rituximab Eye Diseases Central Nervous System Diseases Sclerosis Optic nerve disorder Recurrence Antibodies Paraneoplastic Syndromes Demyelinating Autoimmune Diseases, CNS Myelitis Optic Nerve Diseases Paraneoplastic Syndromes, Nervous System |
Neoplasms Neoplasms by Site Immunologic Factors Immune System Diseases Antineoplastic Agents Therapeutic Uses |
Physiological Effects of Drugs Nervous System Diseases Cranial Nerve Diseases Antirheumatic Agents Pharmacologic Actions |