Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses
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|ClinicalTrials.gov Identifier: NCT02276963|
Recruitment Status : Completed
First Posted : October 28, 2014
Results First Posted : June 6, 2019
Last Update Posted : June 6, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Neuromyelitis Optica Neuromyelitis Optica Spectrum Disorder||Drug: Ublituximab||Phase 1|
The overall objective is to assess the safety of ublituximab as add-on therapy to steroids for treatment of acute optic neuritis and/or 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.
- 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 NMO/NMOSD 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I, Single-Center, Open Label Trial of Ublituximab + Glucocorticoids for the Treatment of Acute Optic Neuritis and/or Transverse Myelitis in Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)|
|Actual Study Start Date :||January 2016|
|Actual Primary Completion Date :||July 2017|
|Actual Study Completion Date :||February 15, 2019|
Experimental: Ublituximab Plus Glucocorticoids
Ublituximab 450 mg intravenously once on day 1, plus glucocorticoids 1000 mg intravenously daily on days 1-5
Monoclonal antibody that specifically binds to the trans-membrane antigen CD20, which induces immune response that causes lysis of B cells.
Other Name: LFB-R603
- Change in Neurological Disability - Expanded Disability Scale Score [ Time Frame: On admission to the hospital on day 1, on discharge 5-21 days later and on follow up at 90 days ]The Kurtzke Expanded Disability Status Scale (EDSS) was developed to measure the disability status of subjects with demyelinating disease. It allows an objective quantification of the level of functioning that could be widely and reproducibly used by researchers and health care providers. The EDSS provides a total score on a scale that ranges from 0 to 10 where 0 is normal and 10 is deceased. Increasing disability is reflected in an increasing EDSS score.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02276963
|United States, Maryland|
|Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Michael Levy, MD, PhD||Johns Hopkins University|