Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00501748
Status:
COMPLETED
Last Update Posted:
2011-09-27
First Post:
2007-07-12
Brief Title:
Safety and Tolerability of Rituximab in Neuromyelitis Optica
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Open Label Study of Safety and Tolerability of Rituximab in Neuromyelitis Optica Recurrent Transverse Myelitis and Recurrent Bilateral Simultaneous Optic Neuritis
Status:
COMPLETED
Status Verified Date:
2011-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
Rituximab is a genetically engineered chimeric murinehuman 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 80 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-Hodgkins 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 opsoclonusmyoclonus
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 46 per 100 patient years For context the rate of infections requiring hospital admission was 957 per 100 patient years in a community based epidemiologic study in RA
We treated 8 patients with NMO with Rituximab and observed that Rituximab appears to be well tolerated with 08 of the patients suffering serious adverse reactions that could be directly related to Rituximab administration Moreover 78 patients experienced decrease in neurological disability following treatment suggesting that B-cell depletion may enhance neurological recovery from attacks 78 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 p0012 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
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-Hodgkins 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 opsoclonusmyoclonus
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 46 per 100 patient years For context the rate of infections requiring hospital admission was 957 per 100 patient years in a community based epidemiologic study in RA
We treated 8 patients with NMO with Rituximab and observed that Rituximab appears to be well tolerated with 08 of the patients suffering serious adverse reactions that could be directly related to Rituximab administration Moreover 78 patients experienced decrease in neurological disability following treatment suggesting that B-cell depletion may enhance neurological recovery from attacks 78 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 p0012 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None