Ublituximab for Multiple Sclerosis

Not currently recruiting at 91 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: TG Therapeutics, Inc.

Must be taking: Ublituximab

Must not be taking: Disease modifying therapy

Disqualifiers: Active infection, Pregnancy, Malignancy, 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: 1

Duration: 312 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the long-term safety and effectiveness of ublituximab for individuals with relapsing multiple sclerosis (RMS). Administered through infusions, the study will monitor its impact on symptoms and disease progression. It seeks participants who have completed previous MS studies with ublituximab and may benefit from continued treatment. Those who have experienced MS relapses and completed specific past studies might find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot start any new disease-modifying therapy or participate in other clinical trials after completing the previous study visits.

Is there any evidence suggesting that ublituximab is likely to be safe for humans?

Research has shown that ublituximab is generally safe for people with relapsing multiple sclerosis (RMS). In a large study, 55.8% of patients who took ublituximab reported infections, but most were mild to moderate. This indicates that while infections can occur, they are usually not serious.

Long-term studies over six years have indicated that ublituximab does not lead to significant disability in most patients. This suggests that although some side effects like infections can happen, the treatment is considered safe for long-term use.

For those considering joining a trial, it is reassuring to know that ublituximab has undergone thorough testing. Most side effects are manageable, and serious problems are rare. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Ublituximab is unique because it targets a specific protein on B-cells, called CD20, which plays a role in multiple sclerosis (MS). Unlike some standard MS treatments that may involve regular oral medication or daily injections, ublituximab is administered via infusions every six months, potentially offering a more convenient dosing schedule. Researchers are excited because this approach might reduce the frequency of relapses and slow disease progression, providing a new option for patients seeking long-term management with fewer treatment sessions.

What evidence suggests that ublituximab might be an effective treatment for multiple sclerosis?

Research shows that ublituximab effectively treats relapsing multiple sclerosis (RMS). Studies have found that patients taking ublituximab experience fewer flare-ups or worsening of symptoms over time. Compared to teriflunomide, all patients on ublituximab had low disease activity by Week 96, while only 30% of those on teriflunomide did. This suggests that ublituximab can greatly reduce disease activity in people with RMS. Long-term studies also confirm its safety, demonstrating positive effects over several years. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people with relapsing multiple sclerosis who completed prior ublituximab studies. They must be willing to use contraception and have no unstable disease activity, malignancies (except certain skin lesions), recent live vaccines, significant medical issues, or ongoing pregnancy. Those who started other MS treatments after previous studies are excluded.

Inclusion Criteria

Female participants of child-bearing potential, and male partners must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for 20 weeks after the last dose of ublituximab

Are able and willing to provide written informed consent (e.g., before the first infusion) and to comply with the study protocol

You must have finished participating in specific previous studies related to this trial.

Exclusion Criteria

I had an MS flare-up in the last month but have been stable for 30 days.

You have started any new treatments or participated in other clinical trials after the specified study visits.

I have not received a live virus vaccine in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ublituximab infusions every 24 weeks for long-term safety and efficacy evaluation

312 weeks

Infusions at Week 1, Week 3, and every 24 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension

Participants continue receiving ublituximab to evaluate long-term safety and efficacy

Up to Week 336

What Are the Treatments Tested in This Trial?

Interventions

• Ublituximab

Trial Overview The study tests the long-term safety and effectiveness of a medication called Ublituximab in individuals with relapsing multiple sclerosis. Participants will receive this drug to see how well it continues to work over time and what side effects may occur with extended use.

How Is the Trial Designed?

Group I: Ublituximab Infusions Experimental Treatment 1 Intervention

RMS301/RMS302: All participants transferring from RMS301/RMS302 who sign consent for this study will receive an initial 4-hour infusion of 150 mg ublituximab on Week 1 (Day 1) followed by a 1-hour infusion of 450 mg ublituximab 14 days later Week 3 (Day 15). Subsequent infusions of ublituximab will be administered at 450 mg for 1-hour every 24 weeks from Weeks 24 to 312. RMS201E: All participants transferring from RMS201E who sign consent for this study will receive a 1-hour infusion of 450 mg ublituximab on Week 1 (Day 1) and subsequent infusions of ublituximab will be administered at 450 mg for 1-hour every 24 weeks from Weeks 24 to 312. For all participants (RMS301/RMS302/RMS201E), infusion treatment will continue for 312 weeks, or until physician or participant decision to withdraw from the study.

Ublituximab is already approved in United States, European Union for the following indications:

Approved in United States as Briumvi for:

• Relapsing forms of multiple sclerosis

Approved in European Union as Briumvi for:

• Relapsing forms of multiple sclerosis in adult patients

Who Is Running the Clinical Trial?

TG Therapeutics, Inc.

Lead Sponsor

Trials

41

Recruited

6,900+

Published Research Related to This Trial

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 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]

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]

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]

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 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 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, 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]

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 ... Patients on continuous BRIUMVI treatment exhibited low and decreasing annualized relapse rate (ARR) throughout the observation period, ARR: ...

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

MS Clinical Trial Results | BRIUMVI® (ublituximab-xiiy) HCP Long-Term Efficacy and Safety of Ublituximab in Relapsing Multiple Sclerosis: Results from 6 Years of ULTIMATE I and II Open-Label Extension. Presented at ...

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/NCT06433765

NCT06433765 | A Study Evaluating the Effect of BRIUMVI® ... A Study Evaluating the Effect of BRIUMVI® (Ublituximab) on Pregnancy and Infant Outcomes in Participants With Multiple Sclerosis (MS). ClinicalTrials.gov ID ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06433752

NCT06433752 | A Study Evaluating the Real World ... The purpose of this study is to evaluate safety, effiectiveness, and to gain insight into the treatment experience of participants prescribed BRIUMVI® ...