Ublituximab for Multiple Sclerosis

(U-PACE Trial)

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test if ublituximab changes walking functions and fall risk in people with relapsing multiple sclerosis (RMS). Twenty-five qualified people with RMS will undergo a 48-week ublituximab treatment. Before, 24 weeks into, and after the treatment, their ambulatory function, disability status, and cognition will be assessed. Additionally, they will experience large-scale slip perturbations on a treadmill under the protection of a safety harness at the last assessment. The outcome measures will be compared across the assessments to examine the effects of ublituximab on improving their walking function, disability status, cognition, and the responses to the unexpected slip perturbation.

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.

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. ^{1 4 5 6 7}

What makes the drug ublituximab unique for treating multiple sclerosis?

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 3 4 5 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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. 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. 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]