Study of Ublituximab for Ocrelizumab Wearing-Off in Multiple Sclerosis

NCT07389590 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: IRB00449860
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 phenomenon.

Conditions

Multiple Sclerosis

Keywords

wearing off; ocrelizumab; ublituximab

Outcome Measures

Primary Outcomes (1)

• 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 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.

  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

  From month 1 up to 11 months

Study Arms (2)

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.

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.

Drug: Ocrelizumab

Interventions

Ublituximab DRUG

Ublituzimab will be administered via IV infusion as specified throughout the study period.

Ublituximab

Ocrelizumab DRUG

Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.

Ocrelizumab

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• TG Therapeutics, Inc.: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ublituximab; ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Shiv Saidha, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ziyun Research Program Coordinator

CONTACT

410-614-1522; zwang306@jhu.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 5, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)