Ublituximab for Multiple Sclerosis

(ENHANCE Trial)

Recruiting at 46 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

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment called ublituximab, a monoclonal antibody, for individuals with Relapsing Multiple Sclerosis (RMS), a condition where the immune system mistakenly attacks the brain and spine. The study will test different doses and schedules to assess their impact on brain lesions, which are areas of damage. Participants will be divided into groups, with some receiving varying doses of the treatment and others receiving a placebo, a harmless substance used for comparison. Individuals diagnosed with RMS who experience frequent relapses might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ublituximab has a known safety record from earlier studies in people with relapsing multiple sclerosis (RMS). The most common side effects include infusion reactions, which occur when the treatment enters the bloodstream, and upper respiratory tract issues, such as colds or sore throats.

Additionally, five-year data shows promising results, but serious infections, including three deaths related to infections, occurred in controlled trials. Although these events are rare, they highlight the need for careful monitoring during treatment.

Overall, ublituximab is generally well-tolerated, suggesting it could be a safe option for many people. However, individual experiences can vary, so discussing any concerns with a healthcare provider is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ublituximab for treating multiple sclerosis (MS) because it offers a novel approach compared to existing treatments like interferons, glatiramer acetate, and ocrelizumab. Unlike these standard therapies, ublituximab targets a specific protein called CD20 on B cells, which play a critical role in the immune system's attack on the nervous system in MS. By depleting these B cells more effectively, ublituximab may offer enhanced efficacy and potentially fewer side effects. Additionally, the treatment's infusion schedule is designed to be more patient-friendly, with fewer clinic visits compared to some current therapies. This dual promise of improved effectiveness and convenience is generating a lot of enthusiasm among researchers.

What evidence suggests that this trial's treatments could be effective for Multiple Sclerosis?

Research has shown that ublituximab effectively treats relapsing multiple sclerosis (RMS). One study revealed that 89.9% of patients with RMS did not experience worsening disability after six years. Another study found that ublituximab significantly reduced disease activity, with all patients achieving low activity levels by Week 96. In this trial, participants will receive different regimens of ublituximab, with some receiving a combination of ublituximab and placebo. These findings suggest that ublituximab can help manage RMS symptoms and slow its progression. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Part B: Ublituximab /Placebo (Treatment Arm A) Experimental Treatment 2 Interventions

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.

Group II: Part B: Ublituximab (Treatment Arm B) Experimental Treatment 1 Intervention

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

Group III: Part A: Ublituximab Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

TG Therapeutics, Inc.

Lead Sponsor

Trials

41

Recruited

6,900+

Published Research Related to This Trial

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]

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]

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, 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]

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 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]

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]

Citations

1. ir.tgtherapeutics.com ir.tgtherapeutics.com/news-releases/news-release-details/new-data-briumvir-demonstrate-899-patients-relapsing-multiple

New Data for BRIUMVI® Demonstrate 89.9% of Patients ... New Data for BRIUMVI® Demonstrate 89.9% of Patients with Relapsing Multiple Sclerosis Were Free from Disability Progression After 6 Years of ...

2. briumvihcp.com briumvihcp.com/efficacy-data/

MS Clinical Trial Results | BRIUMVI® (ublituximab-xiiy) HCP Improvements in no evidence of disease activity with ublituximab vs. teriflunomide in the ULTIMATE phase 3 studies in relapsing multiple sclerosis. Front ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12534265/

Efficacy and safety of ublituximab for relapsing multiple ... Ublituximab significantly reduced DA scores, with 100% of RMS patients achieving low DA scores by Week 96, compared to 30% in the teriflunomide ...

4. tgtherapeutics.com tgtherapeutics.com/publications/long-term-efficacy-and-safety-of-ublituximab-in-relapsing-multiple-sclerosis-results-from-6-years-of-ultimate-i-and-ii-open-label/

Long-Term Efficacy and Safety of Ublituximab in Relapsing ... Long-Term Efficacy and Safety of Ublituximab in Relapsing Multiple Sclerosis: Results from 6 Years of ULTIMATE I and II Open-Label.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06433752

NCT06433752 | A Study Evaluating the Real World ... A Study Evaluating the Real World Experience of Participants Treated With BRIUMVI® (Ublituximab-xiiy) for Relapsing Multiple Sclerosis (RMS) (ENABLE).

6. briumvihcp.com briumvihcp.com/safety-tolerability/

Established Safety Profile | BRIUMVI® (ublituximab-xiiy) HCP Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761238s000lbl.pdf

Briumvi - accessdata.fda.gov There were 3 infection-related deaths that occurred in controlled clinical trials in patients with relapsing forms of multiple sclerosis (RMS), all in patients ...