Ublituximab for Multiple Sclerosis

(ENHANCE Trial)

Recruiting at 32 trial locations

Overseen By Mimi Crum

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: TG Therapeutics, Inc.

Must not be taking: Ublituximab, Alemtuzumab

Disqualifiers: PPMS, Active chronic immune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 51

Duration: 24 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this phase 3b study is to assess the efficacy of a modified regimen of ublituximab as measured by T1 Gadolinium (Gd)-enhancing lesions.

Will I have to stop taking my current medications?

The trial requires that participants who have been treated with a disease-modifying therapy (DMT) must stop their treatment before joining the study and meet specific washout requirements (time without taking certain medications). If you are currently on a DMT, you will need to discontinue it before participating.

What data supports the effectiveness of the drug Ublituximab for treating multiple sclerosis?

Research shows that Ublituximab, a drug that targets B-cells, is effective in reducing the relapse rate in people with relapsing multiple sclerosis. In clinical trials, it was found to be more effective than another drug, Teriflunomide, in decreasing the frequency of relapses and improving MRI outcomes. ^{1 2 3 4 5}

Is Ublituximab safe for humans?

Ublituximab, also known as Briumvi, is a treatment for multiple sclerosis that has been approved in the USA, indicating it has undergone safety evaluations. It works by targeting B cells, which are part of the immune system, and is similar to other treatments like rituximab, which have been studied for safety in multiple sclerosis. ^{1 4 5 6 7}

How is the drug ublituximab different from other treatments for multiple sclerosis?

Ublituximab is unique because it is the first anti-CD20 treatment for multiple sclerosis that is administered as a one-hour infusion twice a year after initial doses, targeting B cells which play a key role in the disease. This makes it different from other treatments that may have more frequent dosing schedules or different mechanisms of action. ^{1 3 4 5 8}

Eligibility Criteria

This trial is for people with Relapsing Multiple Sclerosis (RMS) who've been stable on anti-CD20 therapy like ocrelizumab or rituximab. They should have an EDSS score ≤ 5.5 and diagnosed within the last 10 years. Exclusions include recent relapses, certain infections, vaccine restrictions, IVIG treatments in the past year, severe infusion reactions to previous therapies, and other active immune diseases.

Inclusion Criteria

I have been diagnosed with RMS according to the latest criteria.

My neurological condition has been stable for over a month.

Participants that are currently being treated with other selected DMTs

Exclusion Criteria

I haven't received any live vaccines in the last 4 weeks.

My condition is either PPMS or inactive SPMS.

I have or had hepatitis B or C, but if C, my PCR test for the virus is negative.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a modified regimen of ublituximab with infusions on Day 1 of Week 1, Day 15 if applicable, and at Week 24

24 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Regular monitoring up to Week 48

Treatment Details

Interventions

• Ublituximab

Trial Overview The study tests if switching from current anti-CD20 therapies to Ublituximab maintains its effectiveness against MS. Effectiveness is measured by checking brain lesions using a special MRI scan that highlights active inflammation.

Participant Groups

Group I: Ublituximab Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

TG Therapeutics, Inc.

Lead Sponsor

Trials

41

Recruited

6,900+

Findings from Research

Ublituximab is a newly approved anti-CD20 monoclonal antibody for treating multiple sclerosis (MS), specifically designed to deplete B cells, which play a crucial role in the disease's progression.

It is unique as it requires only two infusions per year after initial doses, making it a convenient treatment option for adults with relapsing forms of MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ublituximab: First Approval. Lee, A.[2023]

Ublituximab, an anti-CD20 antibody, significantly reduces the annualized relapse rate (ARR) in patients with relapsing multiple sclerosis, showing a favorable effect size in a meta-analysis of 1,094 participants.

MRI results at 96 weeks indicate that Ublituximab leads to a greater reduction in T1 and T2 lesions compared to Teriflunomide, and patients on Ublituximab experience less disease activity overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Ublituximab compared to Teriflunomide for relapsing multiple sclerosis: A meta-analysis. Mukhtar, H., Yasmeen, U., Siddiqa, S., et al.[2022]

In two phase 3 trials involving 1,094 participants with relapsing multiple sclerosis, ublituximab significantly reduced the annualized relapse rate compared to teriflunomide, demonstrating its efficacy in preventing relapses.

Ublituximab also resulted in fewer gadolinium-enhancing lesions on MRI, indicating better control of disease activity, although it did not significantly lower the risk of worsening disability and was associated with infusion-related reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. Steinman, L., Fox, E., Hartung, HP., et al.[2022]

Ublituximab is a newly FDA-approved treatment for relapsing forms of Multiple Sclerosis (MS) that effectively depletes B cells while preserving long-lived plasma cells, distinguishing it from other anti-CD20 monoclonal antibodies.

In phase 3 clinical trials (ULTIMATE I and II), ublituximab was compared to teriflunomide, highlighting its potential for different clinical outcomes due to variations in dosing, administration routes, and mechanisms of action among anti-CD20 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis. Boldrini, VO., Mader, S., Kümpfel, T., et al.[2023]

Ublituximab, a monoclonal antibody targeting B-cells, was found to be more effective than teriflunomide in reducing the annualized relapse rates in patients with relapsing multiple sclerosis, based on the ULTIMATE I and II trials.

While ublituximab showed superior efficacy in reducing relapse rates and MRI endpoints, further long-term studies are needed to assess its safety, and it is still under FDA review.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ULTIMATE trials: are there advantages of ublituximab over teriflunomide in relapsing multiple sclerosis? Doggrell, SA.[2022]

Rituximab treatment in patients with multiple sclerosis (MS) led to a significant decrease in the Expanded Disability Status Scale (EDSS) score, indicating improved disability status after treatment, based on a synthesis of 27 studies.

The treatment showed an acceptable safety profile, with a pooled prevalence of side effects at 28.63%, including a 24% prevalence of infections, but further randomized studies with larger sample sizes are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in multiple sclerosis: a systematic review and meta-analysis. Nabizadeh, F., Ahmadabad, MA., Mohamadi, M., et al.[2023]

In a study of 1000 patients with multiple sclerosis (MS) and related disorders treated with rituximab, the rates of serious safety events (SSEs) such as infections and lymphopenia were found to be relatively low, with specific incidence rates per 1000 person-years for lymphopenia at 19.2 and infections at 38.6.

Risk factors for infections included longer duration of therapy, male gender, increased disability, and prior immunosuppression, highlighting the importance of careful monitoring and risk assessment in patients undergoing B-cell depleting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious safety events in rituximab-treated multiple sclerosis and related disorders. Vollmer, BL., Wallach, AI., Corboy, JR., et al.[2021]

Ublituximab is an effective and rapid-acting anti-inflammatory treatment for relapsing forms of multiple sclerosis (MS), significantly reducing the annualized relapse rate and MRI-based disease activity based on Phase 2 and Phase 3 trial data.

However, ublituximab did not show a significant reduction in confirmed disability progression or whole-brain atrophy compared to teriflunomide, indicating that while it is effective in reducing relapses, its impact on long-term disability may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ublituximab-xiiy as a treatment option for relapsing multiple sclerosis. Jakimovski, D., Weinstock-Guttman, B., Zivadinov, R.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ublituximab: First Approval. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of Ublituximab compared to Teriflunomide for relapsing multiple sclerosis: A meta-analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The ULTIMATE trials: are there advantages of ublituximab over teriflunomide in relapsing multiple sclerosis? [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in multiple sclerosis: a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Serious safety events in rituximab-treated multiple sclerosis and related disorders. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Ublituximab-xiiy as a treatment option for relapsing multiple sclerosis. [2023]