Clinical Trial: Safety and Tolerability of Rituximab in Neuromyelitis Optica

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Open Label Study of Safety and Tolerability of Rituximab in Neuromyelitis Optica, Recurrent Transverse Myelitis and Recurrent Bilateral Simultaneous Optic Neuritis

Brief Summary: 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 treatment candidate for this disease.

Detailed Summary:

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 epid
Sponsor: University of California, San Francisco

Current Primary Outcome: Safety and Tolerability of Rituximab in NMO (monitor for any AE during two years of follow up) [ Time Frame: 96 weeks ]

Original Primary Outcome: Safety and Tolerability of Rituximab in NMO (monitor for any AE during two years of follow up) [ Time Frame: 60 weeks ]

Current Secondary Outcome:

  • Time from treatment to recurrence of either optic neuritis or myelitis [ Time Frame: 96 weeks ]
  • Change in Kurtzke expanded disability status scale (EDSS) at weeks 4, 12, 24, 48, 72, 96 [ Time Frame: 96 weeks ]


Original Secondary Outcome:

  • Time from treatment to recurrence of either optic neuritis or myelitis [ Time Frame: 60 weeks ]
  • Change in Kurtzke expanded disability status scale (EDSS) at weeks 4, 12, 24, 48, 72, 96 [ Time Frame: 60 weeks ]


Information By: University of California, San Francisco

Dates:
Date Received: July 12, 2007
Date Started: January 2004
Date Completion:
Last Updated: September 23, 2011
Last Verified: September 2011