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

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

Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab (NCT05877963) is a Phase 3 interventional studying Relapsing Multiple Sclerosis, sponsored by TG Therapeutics, Inc.. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Relapsing Multiple Sclerosis, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 800 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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 weakened immune system 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

BIOLOGICAL

Ublituximab

Administered as an intravenous (IV) infusion.

DRUG

Placebo

IV infusion

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.