Neuromyelitis Optica Clinical Trial
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)
Verified date | June 2019 |
Source | Johns Hopkins University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 6 |
Est. completion date | February 15, 2019 |
Est. primary completion date | July 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility |
Inclusion Criteria: 1. Able and willing to provide written informed consent. 2. 18-100 years of age. 3. 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. 4. 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. 5. 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. 6. 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 7. 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 - Percutaneous contraceptive patches - Intrauterine device (IUD) or intrauterine system (IUS) - Male partner sterilization - Double barrier method Exclusion Criteria: 1. 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 2. History of clinically significant central nervous system (CNS) trauma (e.g. spinal cord compression). 3. Past or current history of medically significant adverse effects from: - Corticosteroids - Diphenhydramine - Murine or mouse/human chimeric antibodies 4. 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. 5. Significant concurrent, uncontrolled medical condition including, but not limited to, cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric, or neurological disease which could affect the subject's safety, impair the subject's reliable participation in the trial, impair the evaluation of endpoints, or necessitate the use of medication not allowed by the protocol, as determined by the PI of the trial. 6. Use of an investigational drug or other experimental therapy for a condition other than NMO within 4 weeks, 5 pharmacokinetic half lives or duration of biological effect (whichever is longer) prior to screening. 7. Current participation in any other interventional clinical trial. Participation in non-interventional trial requires approval of the protocol by investigator. 8. Subjects who are concurrently receiving any other investigational agents, or have participated in an interventional clinical trial within the last 21 days, or subjects who have been vaccinated with a live vaccine < 2 months prior to trial inclusion. 9. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ublituximab breastfeeding should be discontinued if the mother is treated with ublituximab. |
Country | Name | City | State |
---|---|---|---|
United States | Johns Hopkins University School of Medicine | Baltimore | Maryland |
Lead Sponsor | Collaborator |
---|---|
Johns Hopkins University |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 |
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