Neuromyelitis OpticaPhase 1NCT02276963
Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses
A Phase 1 study testing Ublituximab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder
- What is being tested?
- Ublituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 15 Feb 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to provide written informed consent.
- 18-100 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:
Show all 19Show fewer
- 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
- Percutaneous contraceptive patches
- Intrauterine device (IUD) or intrauterine system (IUS)
- Male partner sterilization
- Double barrier method
Who cannot join
- 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
Show all 20Show fewer
- 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.
- 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.
- 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.
- Current participation in any other interventional clinical trial. Participation in non-interventional trial requires approval of the protocol by investigator.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
About this study
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)
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.
Read the detailed description
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.
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 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.
- Being tested
- Ublituximab
- Keywords
- Transverse myelitis, optic neuritis, neuromyelitis optica
- Medical subject headings
- Neuromyelitis Optica, Myelitis, Transverse, Optic Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabDrug
Also called LFB-R603
Monoclonal antibody that specifically binds to the trans-membrane antigen CD20, which induces immune response that causes lysis of B cells.
| Study group | Role | What they receive |
|---|---|---|
| Ublituximab Plus Glucocorticoids | Experimental | Ublituximab 450 mg intravenously once on day 1, plus glucocorticoids 1000 mg intravenously daily on days 1-5 Receives: Drug: Ublituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: On admission to the hospital on day 1, on discharge 5-21 days later and on follow up at 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startJan 2016
- Primary completionJul 2017
- Study completion15 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuromyelitis OpticaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Levy, MD, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276963
- Sponsor's protocol ID
- IRB00052958
- Status last verified
- Jun 2019
- First submitted
- 21 Oct 2014
- Last updated
- 6 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02276963
- Acronym / sponsor ID
- IRB00052958
- Keywords
- Transverse myelitis, optic neuritis, neuromyelitis optica
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- 15 Feb 2019 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Posted 6 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ublituximab Plus Glucocorticoids | Experimental | Drug: UblituximabUblituximab 450 mg intravenously once on day 1, plus glucocorticoids 1000 mg intravenously daily on days 1-5 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Able and willing to provide written informed consent.
- 18-100 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.
Key exclusion criteria (20 listed)
- Current evidence or known history of clinically significant infection including:
- History of clinically significant central nervous system (CNS) trauma (e.g. spinal cord compression).
- Past or current history of medically significant adverse effects from:
- Past or current malignancy, except for
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UblituximabAlso: LFB-R603Monoclonal antibody that specifically binds to the trans-membrane antigen CD20, which induces immune response that causes lysis of B cells. | Drug | Ublituximab Plus Glucocorticoids |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Levy, MD, PhD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ublituximab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2019.