Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab (ENHANCE)

May 27, 2026 updated by: TG Therapeutics, Inc.

Evaluating Safety, Efficacy and Pharmacokinetics of a Modified Regimen of Ublituximab (ENHANCE )

The primary purpose of this phase 3b study is to assess the efficacy of a modified regimen of ublituximab in participants with relapsing multiple sclerosis (RMS) as measured by T1 Gadolinium (Gd)-enhancing lesions in Part A; PK in Part B along with efficacy of ublituximab as measured by T1 Gd-enhancing lesions in participants who had a suboptimal experience on prior anti-CD20 therapy in Part C. The study consists of 3 parts: Part A is single-armed and open-label, Part B is randomized, double-blind, placebo-controlled, and Part C is single-armed and open-label.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

800

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Poland
      • Bydgoszcz, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Katowice, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Katowice, Poland, 40-555
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Kielce, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Krakow, Poland, 31-826
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Lodz, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Olsztyn, Poland, 10-561
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Poznan, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Warsaw, Poland, 04-141
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Zabrze, Poland
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Żory, Poland, 44-240
        • Recruiting
        • TG Therapeutics Investigational Trial Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Cullman, Alabama, United States, 35058
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • California
      • Orange, California, United States, 92697
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Colorado
      • Fort Collins, Colorado, United States, 80528
        • Recruiting
        • TG Investigational Site
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Georgia
      • Savannah, Georgia, United States, 31406
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Indiana
      • Indianapolis, Indiana, United States, 46256
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Kansas
      • Overland Park, Kansas, United States, 66212
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Maryland
      • Lutherville, Maryland, United States, 21093
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 00002
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Foxborough, Massachusetts, United States, 02035
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • North Worcester, Massachusetts, United States, 01655
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Wellesley, Massachusetts, United States, 02481uni
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Michigan
      • Farmington, Michigan, United States, 48334
        • Recruiting
        • TG Investigational Site
    • Minnesota
      • Golden Valley, Minnesota, United States, 55422
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Plymouth, Minnesota, United States, 55446
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Missouri
      • St Louis, Missouri, United States, 63131
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • New York
      • New York, New York, United States, 10025
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • New York, New York, United States, 11021
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • TG Therapeutics Investigational Trial SiteCharlotte
      • Raleigh, North Carolina, United States, 27607
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Dayton, Ohio, United States, 45417
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37922
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • TG Therapeutics Investigational Trial Site
    • Utah
      • Salt Lake City, Utah, United States, 84103
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Virginia
      • Vienna, Virginia, United States, 22182
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Washington
      • Kirkland, Washington, United States, 98034
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Seattle, Washington, United States, 98109
        • Recruiting
        • TG Therapeutics Investigational Trial Site
      • Spokane, Washington, United States, 99208
        • Recruiting
        • TG Therapeutics Investigational Trial Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • TG Therapeutics Investigational Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of RMS (2017 Revised McDonald criteria).

  • Participants must meet one of the following prior treatment definitions:

    1. Participants naïve to treatment.
    2. Participants previously treated with a disease modifying therapy (DMT) who have discontinued treatment prior to consent and meet the washout requirements.
  • Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening.
  • Neurologically stable for > 30 days prior to first dose of ublituximab.
  • Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for 6 months after the last dose of ublituximab.
  • Part C: participants currently treated with an anti-CD20 agent for at least 6 months and meet the washout requirements prior to W1D1.
  • Part C: Discontinuation of current anti-CD20 must be due to suboptimal experience

Exclusion Criteria:

  • History of any serious 3 Infusion Related Reaction (IRR) on prior anti-CD20 therapy.
  • Primary-progressive multiple sclerosis (PPMS) or inactive Secondary Progressive MS (SPMS).
  • Active chronic (or stable but treated with immune therapy) disease of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency, etc.).
  • Current evidence or known history of clinically significant infection, including: chronic, recurrent, or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to chronic urinary tract infection, chronic pulmonary infection with bronchiectasis, tuberculosis, or active hepatitis C virus (HCV).
  • Previous serious opportunistic or atypical infection.
  • Evidence of chronic active or history of hepatitis B virus (HBV) infection as evidenced by a detectable hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody (HBcAb), or chronic hepatitis C infection. Participants with positive hepatitis C virus antibody (HCV Ab) are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
  • History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML).
  • Receipt of any live or live-attenuated vaccines (including vaccines for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration.
  • Participants requiring treatment with intravenous immune globulin (IVIG) for decreased immunoglobulins within the 12 months prior to W1D1.
  • Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma.
  • Participants who have ever received ublituximab, alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab (including for non-MS indications).

Note: Other Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Ublituximab

Participants will receive a modified regimen of ublituximab including infusions on Day 1 of Week 1 (W1D1), Day 15, if applicable, and ublituximab 450 milligrams (mg) infusion at Week 24.

With Protocol Version 6.0, enrollment in Part A was closed.
Biological: Ublituximab
Administered as an intravenous (IV) infusion.
Other Names:
  • TG-1101
  • BRIUMVI
Experimental: Part B: Ublituximab /Placebo (Treatment Arm A)

Participants will receive 600 mg of ublituximab on W1D1 followed by a placebo infusion on Day 15 and 450 mg ublituximab infusion at Week 24.

With Protocol Version 7.0, enrollment in Part B will be closed.
Drug: Placebo
IV infusion
Biological: Ublituximab
Administered as an intravenous (IV) infusion.
Other Names:
  • TG-1101
  • BRIUMVI
Experimental: Part B: Ublituximab (Treatment Arm B)

Participants will receive 150 mg of ublituximab on W1D1 followed by 450 mg on Day 15 and at Week 24.

With Protocol Version 7.0, enrollment in Part B will be closed.
Biological: Ublituximab
Administered as an intravenous (IV) infusion.
Other Names:
  • TG-1101
  • BRIUMVI
Experimental: Part C: Ublituximab (Treatment Arm C)
Participants will receive 150 mg of ublituximab on W1D1, followed by 450 mg on Day 15 and at Week 24.
Biological: Ublituximab
Administered as an intravenous (IV) infusion.
Other Names:
  • TG-1101
  • BRIUMVI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A and Part C: Percentage of Participants With no Change or Reduction in Number of T1 Gd-Enhancing Lesions From Baseline to Week 48
Time Frame: Baseline up to Week 48
The Gd-enhancing T1 lesions will be evaluated using magnetic resonance imaging (MRI) technique.
Baseline up to Week 48
Part B: Area Under the Curve Over the First 16 Weeks (AUC0-W16) of Ublituximab
Time Frame: Predose and at multiple timepoints up to Week 16
Predose and at multiple timepoints up to Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Parts A: Percentage of Participants Free of T1 Gd-Enhancing Lesions
Time Frame: Week 48
The Gd-enhancing T1 lesions will be evaluated using MRI technique.
Week 48
Parts A and B: Percentage of Participants Experiencing Infusion Related Reactions (IRRs)
Time Frame: Up to Week 48
IRRs are defined as infusion related adverse events (AEs) that occur within one day of an infusion and resolve within 7 days. IRRs will be reported by investigator.
Up to Week 48
Parts A: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) Scores
Time Frame: Part A: Baseline, Week 24 and Week 48
The TSQM-9 is a 9-item questionnaire with 3 domains: Satisfaction, convenience, and effectiveness.
Part A: Baseline, Week 24 and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TG Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

May 18, 2023

First Submitted That Met QC Criteria

May 18, 2023

First Posted (Actual)

May 26, 2023

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TG1101-RMS401
  • 2024-519284-18-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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