Switching to ublituximab for ocrelizumab wearing-off in multiple sclerosis

A Pilot Study of Ublituximab in People With MS Experiencing Wearing Off Phenomena While Receiving Treatment With Ocrelizumab

This pilot will try switching people with relapsing MS who experience symptom 'wearing off' on ocrelizumab to ublituximab to see if their symptoms improve or return later.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Drugs / interventions: ocrelizumab, ublituximab, rituximab, ofatumumab, alemtuzumab, cyclophosphamide, ublituzimab
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07389590 on ClinicalTrials.gov

What this trial studies

The study enrolls adults with relapsing MS who have been on standard-interval ocrelizumab for at least one year and meet a defined 'wearing off' threshold on Neuro-QoL measures. Eligible participants who are willing may switch from ocrelizumab to ublituximab and will be followed with repeated Neuro-QoL assessments of sleep, fatigue, mood, and limb function across infusion cycles. The protocol compares symptom scores before and after the switch to determine whether wearing-off resolves, improves, or is delayed. Safety and tolerability of switching between these anti-CD20 therapies will also be monitored.

Who should consider this trial

Good fit: Adults aged 18–65 with relapsing forms of MS who have been on standard-interval ocrelizumab for at least one year and show objectively measured wearing-off on Neuro-QoL assessments.

Not a fit: Patients who have previously received other anti-CD20 therapies (such as rituximab or ofatumumab), who do not show measurable Neuro-QoL worsening, or who have progressive MS are unlikely to benefit from this switching approach.

Why it matters

Potential benefit: If successful, switching to ublituximab could reduce or delay the return of MS-related symptoms between ocrelizumab doses for some patients.

How similar studies have performed: This is a relatively novel, pilot approach with limited direct published evidence that switching between anti-CD20 agents resolves wearing-off, although both drugs have demonstrated efficacy in MS.

Eligibility criteria

Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.
* 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.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins University — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Shiv Saidha, MD — Johns Hopkins University
• Study coordinator: Ziyun Research Program Coordinator

Conditions Multiple Sclerosis; wearing off; ocrelizumab; ublituximab