Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses

NCT02276963 | Completed Phase 1 Results DMC

• 1 other identifier: IRB00052958
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder

Keywords

Transverse myelitis, optic neuritis, neuromyelitis optica

Outcome Measures

Primary Outcomes (1)

• Change in Neurological Disability - Expanded Disability Scale Score

  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.

  On admission to the hospital on day 1, on discharge 5-21 days later and on follow up at 90 days

Study Arms (1)

Ublituximab Plus Glucocorticoids

EXPERIMENTAL

Ublituximab 450 mg intravenously once on day 1, plus glucocorticoids 1000 mg intravenously daily on days 1-5

Drug: Ublituximab

Interventions

Ublituximab DRUG

Monoclonal antibody that specifically binds to the trans-membrane antigen CD20, which induces immune response that causes lysis of B cells.

Also known as: LFB-R603

Ublituximab Plus Glucocorticoids

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent.
• years of age.
• New acute optic neuritis and/or transverse myelitis. A clinical event is defined as an episode of inflammation in the spinal cord and/or optic nerve leading to neurologic deficits on physical exam not attributable to another disease process.
• Confirmed or highly suspected diagnosis of NMO according to the 2006 revisions of the Wingerchuk diagnostic criteria for NMO (Wingerchuk, 2006), or AQP4 positive NMOSD.
• The B cell count must be normal (5-20% of total lymphocytes) in subjects who have not received another B cell depleting therapy in the past year. For those on B cell depleting therapy within the past year, a B cell count of at least 0.5% is necessary.
• A female subject is eligible to enter the trial if she is:
• Not pregnant or nursing;
• Of non-childbearing potential OR of child-bearing potential
• Subject has a negative serum pregnancy test at screening and agrees to one of the following:
• Complete abstinence from intercourse for the period from consent into the trial until 6 months after the last dose of investigational product; or,
• Consistent and correct use of one of the following acceptable methods of birth control for the period from consent into the trial until 6 months after the last dose of investigational product:
• Oral contraceptives
• Injectable progesterone
• Levonorgestrel implants
• Estrogenic vaginal ring

You may not qualify if:

• Current evidence or known history of clinically significant infection including:
• Chronic or ongoing active infectious disease
• Previous serious opportunistic or atypical infections.
• Hepatitis B
• Tuberculosis (TB)
• HIV
• History of clinically significant central nervous system (CNS) trauma (e.g. spinal cord compression).
• Past or current history of medically significant adverse effects from:
• Corticosteroids
• Diphenhydramine
• Murine or mouse/human chimeric antibodies
• Past or current malignancy, except for
• Cervical carcinoma Stage 1B or less
• Non-invasive basal cell and squamous cell skin carcinoma
• Cancer diagnoses with a duration of complete response (remission) \>5 years A history of hematologic malignancy excludes a subject from participation, regardless of response.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Neuromyelitis Optica; Myelitis, Transverse; Optic Neuritis

Interventions

ublituximab; LFB-R603

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis; Central Nervous System Infections; Infections; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Central Nervous System Diseases; Spinal Cord Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases

Results Point of Contact

• Title: Michael Levy
• Organization: Johns Hopkins University

mlevy@jhmi.edu

443-287-4412

Study Officials

• Michael Levy, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 28, 2014
• Study Start: January 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: February 15, 2019
• Last Updated: June 6, 2019
• Results First Posted: June 6, 2019

Record last verified: 2019-06

Locations

US (1)