Ublituximab for Multiple Sclerosis

(U-PACE Trial)

Not yet recruiting at 1 trial location

Overseen By Mittie Mitchell, RN, CRC

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Georgia State University

Must not be taking: Corticosteroids, Immunosuppressants, Anti-CD20

Disqualifiers: Other MS types, Liver disease, Infections, Psychiatric disorders, others

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

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

Compensation: Varies

Number of Visits: 4

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new treatment, ublituximab (also known as Briumvi), can help people with relapsing multiple sclerosis (RMS) improve their walking and reduce their risk of falling. Participants will receive treatment for 48 weeks, with assessments of walking, disability level, and thinking skills at various points. The trial seeks individuals with RMS who can walk at least 25 feet independently and stand alone for 30 seconds. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before participating. Specifically, you cannot have taken systemic corticosteroids within 4 weeks prior to screening, and certain other treatments like cyclophosphamide or azathioprine within 24 months prior. Check with the trial team to see if your current medications are on the exclusion list.

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

Research shows that ublituximab is generally well-tolerated by people with relapsing multiple sclerosis (RMS). Studies have found that the most common side effects include infusion reactions and upper respiratory infections, occurring in at least 10% of patients. It's important to note that earlier clinical trials reported three deaths related to infections, though these were rare.

The FDA has approved ublituximab for treating RMS, indicating it has passed strict safety checks for this condition. This approval suggests that while some risks exist, the treatment is considered safe for many patients. In a trial, doctors will closely monitor participants to ensure safety and manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ublituximab is unique because it targets a specific protein called CD20 on B-cells, which are a type of immune cell involved in multiple sclerosis (MS). This mechanism is different from many standard MS treatments, such as interferons and glatiramer acetate, which mainly modulate or suppress the immune response more broadly. Researchers are excited about ublituximab because its targeted approach may offer a more effective way to reduce disease activity with potentially fewer side effects. Additionally, the use of monoclonal antibodies like ublituximab represents a growing trend in precision medicine, aiming to provide tailored and efficient treatment options for MS patients.

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

Research has shown that ublituximab, which participants in this trial will receive, holds promise for treating relapsing multiple sclerosis (RMS). In earlier studies, 89.9% of patients who received ublituximab did not experience any worsening of their disability over six years. Another study found that by week 96, all patients had low disease activity, compared to only 30% of those taking teriflunomide, another treatment option. These results suggest that ublituximab effectively reduces disease activity and progression in people with RMS. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for 25 people with relapsing multiple sclerosis (RMS). Participants should be able to walk and have a certain level of disability. Details on specific inclusion or exclusion criteria are not provided, but typically these would outline who can safely participate.

Inclusion Criteria

Women of childbearing potential must agree to remain abstinent or use contraception with a failure rate of < 1% per year or a barrier method supplemented with spermicide

Ability to provide written, informed consent and to be compliant with the schedule of protocol assessments

Can read and understand English

Exclusion Criteria

Hypersensitive to any of the ingredients of ublituximab

I do not have any severe illnesses that could stop me from joining.

My MS type is not relapsing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants' ambulatory functions, disease progression, and cognitive function are assessed before treatment

1 week

1 visit (in-person)

Treatment

Participants receive a 48-week ublituximab treatment with assessments at weeks 0, 24, and 48

48 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including fall tracking for 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ublituximab

Trial Overview The study tests ublituximab's effect on walking function and fall risk in RMS patients over a period of 48 weeks. It includes assessments of ambulatory function, disability status, cognition, and response to slip perturbations while walking on a treadmill.

How Is the Trial Designed?

Group I: Ublituximab Experimental Treatment 1 Intervention

This arm will receive a 48-week ublituximab treatment.

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?

Georgia State University

Lead Sponsor

Trials

71

Recruited

33,600+

Atlanta Neuroscience Institute

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

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]

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, 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]

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 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]

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]

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. 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).

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000210671

Five Years of Ublituximab in Relapsing Multiple Sclerosis In ULTIMATE I and II studies, ublituximab (UBL) demonstrated significant reduction in disease activity vs. teriflunomide (TER) over 2 years.

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 ...

8. briumvi.com briumvi.com/

Relapsing MS Treatment | BRIUMVI® (ublituximab-xiiy) BRIUMVI® (ublituximab-xiiy) is indicated for the treatment of relapsing multiple sclerosis. See safety info and full Prescribing Information.