Ignite Creation Date:
2024-05-06 @ 3:21 AM
Last Modification Date:
2024-10-26 @ 11:32 AM
Study NCT ID:
NCT02276963
Status:
COMPLETED
Last Update Posted:
2019-06-06
First Post:
2014-10-21
Brief Title:
Ublituximab for Acute Neuromyelitis Optica NMO Relapses
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
Phase I Single-Center Open Label Trial of Ublituximab Glucocorticoids for the Treatment of Acute Optic Neuritis andor Transverse Myelitis in Neuromyelitis Optica NMO and Neuromyelitis Optica Spectrum Disorder NMOSD
Status:
COMPLETED
Status Verified Date:
2019-06
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:
Ublituximab also known as LFB-R603 is a monoclonal antibody that specifically binds to the trans-membrane antigen CD20 The binding induces immune response that causes lysis of B cells
The rationale for using ublituximab in neuromyelitis optica NMO and neuromyelitis optica spectrum disorder NMOSD is based on the known roles of B cells antibody production and plasma cells in the pathophysiology of NMO NMO is characterized by the presence of an anti-Aquaporin-4 AQP4 antibody which can only be produced by differentiation of B cells to plasma cells Because these anti-AQP4 antibodies may be pathogenic B cells recognizing AQP4 may be directly involved in the disease process as well B cells also play a role as potent antigen presenting cells in NMO The strongest evidence of the importance of B cells in NMO comes from studies of B cell depletion most commonly with anti-CD20 monoclonal antibody rituximab Rituxan
Rituximab has been shown in five retrospective and two prospective studies to be effective in reducing NMO relapses up to 90 and achieving remission in up to 80 of patients solely by its action on CD20 B cells despite no change in plasma cell population and anti-AQP4 antibody titers These human trials strongly suggest a critical role for B cells in the pathophysiology of human disease While typically used in the prevention of disease B-cell depletion may be beneficial in the treatment of an acute relapse as well Emerging evidence indicates that peripheral B cells are activated during a relapse and plasmablast production of anti-AQP4 antibodies spikes B cells are also found within acute lesions of the spinal cord and optic nerve suggesting roles both in the blood and in the central nervous system during a relapse
The rationale for using ublituximab in neuromyelitis optica NMO and neuromyelitis optica spectrum disorder NMOSD is based on the known roles of B cells antibody production and plasma cells in the pathophysiology of NMO NMO is characterized by the presence of an anti-Aquaporin-4 AQP4 antibody which can only be produced by differentiation of B cells to plasma cells Because these anti-AQP4 antibodies may be pathogenic B cells recognizing AQP4 may be directly involved in the disease process as well B cells also play a role as potent antigen presenting cells in NMO The strongest evidence of the importance of B cells in NMO comes from studies of B cell depletion most commonly with anti-CD20 monoclonal antibody rituximab Rituxan
Rituximab has been shown in five retrospective and two prospective studies to be effective in reducing NMO relapses up to 90 and achieving remission in up to 80 of patients solely by its action on CD20 B cells despite no change in plasma cell population and anti-AQP4 antibody titers These human trials strongly suggest a critical role for B cells in the pathophysiology of human disease While typically used in the prevention of disease B-cell depletion may be beneficial in the treatment of an acute relapse as well Emerging evidence indicates that peripheral B cells are activated during a relapse and plasmablast production of anti-AQP4 antibodies spikes B cells are also found within acute lesions of the spinal cord and optic nerve suggesting roles both in the blood and in the central nervous system during a relapse
Detailed Description:
The overall objective is to assess the safety of ublituximab as add-on therapy to steroids for treatment of acute optic neuritis andor transverse myelitis in NMO and NMOSD
Primary Objective To assess safety of acute B cell depletion in NMO subjects with acute relapse of optic neuritis or transverse myelitis who are treated with ublituximab glucocorticoids beginning on dose administration and ending with recovery of B cells
Secondary Objectives
To determine the B cell depletion pharmacokinetics of ublituximab in the NMO patients population with monthly B cell counts for up to 9 months
To determine the frequency of adverse events with ublituximab in this patient population
Trial Design Given the severity and the consequences of relapse in NMO placebo treatment without steroid treatment is unethical and use of an active treatment is considered mandatory The potential of currently utilized drugs and techniques to reduce the inflammation in NMO has been established primarily through expert consensus and small open label and retrospective studies
This is a Phase 1 open-label standard-of-care single treatment arm unblinded single center interventional trial in NMONMOSD patients in which experimental subjects will receive one 1 infusion of 450 mg of intravenous ublituximab at the onset of an NMO exacerbation in addition to standard of care treatment with daily intravenous glucocorticoid at 1000 mg for five days
Primary Objective To assess safety of acute B cell depletion in NMO subjects with acute relapse of optic neuritis or transverse myelitis who are treated with ublituximab glucocorticoids beginning on dose administration and ending with recovery of B cells
Secondary Objectives
To determine the B cell depletion pharmacokinetics of ublituximab in the NMO patients population with monthly B cell counts for up to 9 months
To determine the frequency of adverse events with ublituximab in this patient population
Trial Design Given the severity and the consequences of relapse in NMO placebo treatment without steroid treatment is unethical and use of an active treatment is considered mandatory The potential of currently utilized drugs and techniques to reduce the inflammation in NMO has been established primarily through expert consensus and small open label and retrospective studies
This is a Phase 1 open-label standard-of-care single treatment arm unblinded single center interventional trial in NMONMOSD patients in which experimental subjects will receive one 1 infusion of 450 mg of intravenous ublituximab at the onset of an NMO exacerbation in addition to standard of care treatment with daily intravenous glucocorticoid at 1000 mg for five days
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