Multiple SclerosisPhase 4NCT07389590
Study of Ublituximab for Ocrelizumab Wearing-Off in Multiple Sclerosis
A Phase 4 study testing Ublituximab and Ocrelizumab in people with Multiple Sclerosis, run by Johns Hopkins University at 1 site in United States.
Trial summary
The proposed study is a pilot study of ublituximab involving people with multiple sclerosis (MS) who are experiencing a "wearing off" phenomenon (return or worsening of MS-related symptoms) while being treated with ocrelizumab, and exploring whether switching to ublituzimab can resolve, improve or delay this… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ublituximab and Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2026to Mar 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with relapsing forms of MS.
- Age between 18 and 65 years old (inclusive).
- On treatment with standard interval ocrelizumab for at least one year.
- Eligible and willing to continue treatment with ocrelizumab or ublituximab.
- The presence of wearing off phenomena, defined as either worsening in any Neuro-QoL sleep disturbance, fatigue, depression, upper and lower extremity scores (moving from a lower category of symptom severity to a higher category, based on previously defined cutoff scores), a worsening of Neuro-QoL score of 10 points (which equals 1 SD) or more in any domain between a 1-2 month post-infusion assessment (after one ocrelizumab infusion) and a 1-2 month pre-infusion assessment (before the next scheduled infusion).
Who cannot join
- Prior therapy: Has ever received any of the following:
- B-cell targeted therapies: rituximab, ofatumumab, ublituximab or other anti-CD20 agents besides ocrelizumab.
- Prior use of cladribine, alemtuzumab, mitoxantrone, cyclophosphamide or HSCT.
- Lymphopenia: a lymphocyte count <500/ millimeter (mm)^3. Historical labs may be used if the collection date is 6 months or less prior to deeming eligible.
- Neutrophils <1.5X10E9/L. Historical labs may be used if the collection date is 6 months or less prior to deeming eligible.
- Clinically unstable medical or psychiatric disorder.
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- Substance abuse: has evidence of current drug or alcohol abuse or dependence.
- 365 Day prior therapy: has received a biologic investigational agent other than B-cell targeted therapy [e.g., anti CD40L antibody].
- Malignancy: has a history of malignancy in the past 5 years except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
- Have a history of a primary immunodeficiency.
- Have a significant IgG deficiency (IgG level < 400 mg/dL).
- Have an IgA deficiency (IgA level < 10 mg/dL).
- Infection history:
- Currently on any suppressive therapy for chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria).
- Hospitalization for treatment of infection within 60 days of Screening.
- Use of parenteral (IV or IM) antibiotics (anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60 days of Screening.
- Other disease/conditions: has any of the following: a) clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
- Hepatitis status:
- Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows: Patients positive for HBsAg or HBcAb are excluded.
- A positive test for Hepatitis C antibody
- HIV: known to have a historically positive HIV test or tests positive at screening for HIV.
- Laboratory abnormalities: An abnormal laboratory assessment is made, which is judged clinically significant by the investigator.
- Drug Sensitivity: has a history of sensitivity to any of the study medications.
- Any contraindication to undergoing MRI.
- TB: tests positive at screening for tuberculosis.
- Impaired decision-making capacity or impaired ability to provide informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
About this study
Official title: A Pilot Study of Ublituximab in People With MS Experiencing Wearing Off Phenomena While Receiving Treatment With Ocrelizumab
The proposed study is a pilot study of ublituximab involving people with multiple sclerosis (MS) who are experiencing a "wearing off" phenomenon (return or worsening of MS-related symptoms) while being treated with ocrelizumab, and exploring whether switching to ublituzimab can resolve, improve or delay this phenomenon.
- Conditions
- Multiple Sclerosis
- Being tested
- Ublituximab, Ocrelizumab
- Keywords
- wearing off, ocrelizumab, ublituximab
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabDrug
Ublituzimab will be administered via IV infusion as specified throughout the study period.
OcrelizumabDrug
Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Ublituximab | Experimental | Participants in this arm will switch from Ocrelizumab to receive Ublituximab administered intravenously (IV) as cumulative dose of 450-milligram (mg) infusions every 6 months for at least 2 doses. Receives: Drug: Ublituximab |
| Ocrelizumab | Active comparator | Participants in this arm will continue to receive Ocrelizumab administered intravenously (IV) as 600-milligram (mg) infusions every 6 months for at least a further 2 doses. Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients with Wearing-Off
The proportion of patients with the wearing-off phenomenon (as defined below).
Wearing off is defined as either worsening in any Neuro-QoL (Quality of Life in Neurological Disorders) fatigue, depression, upper and lower extremity scores (moving from a lower category of symptom severity to a higher category, based on previously defined cutoff scores) or 0.5-point worsening in average SymptoMScreen score.
Measured: From month 1 up to 11 months
Secondary outcomes (1)
The Frequency and Severity of Wearing-Off Events as assessed by the number of Neuro-QoL or SymptoMScreen events
The number of Neuro-QoL (Quality of Life in Neurological Disorders) or SymptoMScreen events (as defined below) per patient per infusion cycle that qualifies as a marker of wearing off.
Wearing off events are defined as either worsening in any Neuro-QoL fatigue, depression, upper and lower extremity scores (moving from a lower category of symptom severity to a higher category, based on previously defined cutoff scores) or 0.5-point worsening in average SymptoMScreen score.
Measured: From month 1 up to 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study start10 Feb 2026
- Primary completionOct 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- TG Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Shiv Saidha, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389590
- Sponsor's protocol ID
- IRB00449860
- Status last verified
- May 2026
- First submitted
- 29 Jan 2026
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Ublituximab in People With MS Experiencing Wearing Off Phenomena While Receiving Treatment With Ocrelizumab
- ClinicalTrials.gov ID
- NCT07389590
- Acronym / sponsor ID
- IRB00449860
- Conditions
- Multiple Sclerosis
- Keywords
- wearing off, ocrelizumab, ublituximab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- TG Therapeutics, Inc.
- Study start
- 10 Feb 2026 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 5 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is a pilot study of ublituximab involving people with multiple sclerosis (MS) who are experiencing a "wearing off" phenomenon (return or worsening of MS-related symptoms) while being treated with ocrelizumab, and exploring whether switching to ublituzimab can resolve, improve or delay this phenomenon.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ublituximab | Experimental | Drug: UblituximabParticipants in this arm will switch from Ocrelizumab to receive Ublituximab administered intravenously (IV) as cumulative dose of 450-milligram (mg) infusions every 6 months for at least 2 doses. |
| Ocrelizumab | Active comparator | Drug: OcrelizumabParticipants in this arm will continue to receive Ocrelizumab administered intravenously (IV) as 600-milligram (mg) infusions every 6 months for at least a further 2 doses. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with relapsing forms of MS.
- Age between 18 and 65 years old (inclusive).
- On treatment with standard interval ocrelizumab for at least one year.
- Eligible and willing to continue treatment with ocrelizumab or ublituximab.
- The presence of wearing off phenomena, defined as either worsening in any Neuro-QoL sleep disturbance, fatigue, depression, upper and lower extremity scores (moving from a lower category of symptom severity to a higher category, based on previously defined cutoff scores), a worsening of Neuro-QoL score of 10 points (which equals 1 SD) or more in any domain between a 1-2 month post-infusion assessment (after one ocrelizumab infusion) and a 1-2 month pre-infusion assessment (before the next scheduled infusion).
Key exclusion criteria (26 listed)
- Prior therapy: Has ever received any of the following:
- Lymphopenia: a lymphocyte count <500/ millimeter (mm)^3. Historical labs may be used if the collection date is 6 months or less prior to deeming eligible.
- Neutrophils <1.5X10E9/L. Historical labs may be used if the collection date is 6 months or less prior to deeming eligible.
- Clinically unstable medical or psychiatric disorder.
- Substance abuse: has evidence of current drug or alcohol abuse or dependence.
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 |
|---|---|---|
| UblituximabUblituzimab will be administered via IV infusion as specified throughout the study period. | Drug | Ublituximab |
| OcrelizumabOcrelizumab will be administered via IV infusion as specified throughout the treatment period. | Drug | Ocrelizumab |
Primary outcome
Proportion of Patients with Wearing-Off
Time frame: From month 1 up to 11 months
The proportion of patients with the wearing-off phenomenon (as defined below). Wearing off is defined as either worsening in any Neuro-QoL (Quality of Life in Neurological Disorders) fatigue, depression, upper and lower extremity scores (moving from a lower category of symptom severity to a higher category, based on previously defined cutoff scores) or 0.5-point worsening in average SymptoMScreen score.
1 secondary outcome
The Frequency and Severity of Wearing-Off Events as assessed by the number of Neuro-QoL or SymptoMScreen events
Time frame: From month 1 up to 11 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
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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.
Shiv Saidha, MD 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 4 study testing Ublituximab and Ocrelizumab in people with Multiple Sclerosis, 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 5 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 6 May 2026. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ziyun Research Program Coordinator (410-614-1522, zwang306@jhu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients with Wearing-Off (time frame: From month 1 up to 11 months). 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 May 2026.