Ublituximab for Multiple Sclerosis

Recruiting at 65 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: TG Therapeutics, Inc.

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

1100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate long-term safety and efficacy of ublituximab therapy in participants with relapsing multiple sclerosis (RMS).

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.

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 annual relapse rate in people with relapsing multiple sclerosis. In clinical trials, it was found to be more effective than Teriflunomide, another MS treatment, in reducing disease activity as seen on MRI scans. ^{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. It works by targeting B cells, which are part of the immune system. While the specific safety data for ublituximab is not detailed here, it is similar to other treatments like rituximab, which have been studied for safety in multiple sclerosis. ^{2 3 4 6 7}

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

Ublituximab is unique because it is the first anti-CD20 treatment for multiple sclerosis that is administered as one-hour infusions twice a year after initial doses, targeting B cells which play a key role in the disease. ^{1 2 3 4 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Ublituximab: First Approval. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

7. Italy pubmed.ncbi.nlm.nih.gov

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

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

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