Ublituximab for Multiple Sclerosis

Overseen By Kerry Naunton, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must be taking: B-cell depleting

Must not be taking: B-cell depleting

Disqualifiers: Eye disease, Chronic infection, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the research study is to explore new retinal imaging biomarkers of immune cell activity in MS during use of ublituximab (Briumvi) treatment. A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. This study will evaluate the efficacy of ublituximab to modulate MS pathology in a new manner. In order to assess this new biomarker, a specialized optical coherence tomography (OCT) scan will be performed at enrollment into the study and at 2 other timepoints throughout the study. Subjects asked to take part in this study should have been diagnosed with relapsing multiple sclerosis (MS) and have recently been advised to start the medication ublituximab (Briumvi) or are currently on another medication for the treatment of their MS. We plan to enroll 30 patients into this study. Fifteen (15) patients with Relapsing Remitting Multiple Sclerosis (RRMS) who are being initiated on B-cell depletion therapy by their treating physician at the University of Maryland Center for MS Treatment and Research will be offered enrollment into this study. Additionally, 15 age/sex matched patients with stable RRMS who are not undergoing any change in treatment and are not currently on B-cell depleting therapies will be enrolled as control subjects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are in the Ublituximab group, you should not have been on any B-cell depleting therapies in the past 12 months. If you are in the Comparison group, you should be on a stable dose of your current MS treatment with no plans to change it for the next year.

How is the drug Ublituximab different from other treatments for multiple sclerosis?

Ublituximab is unique because it is an anti-CD20 monoclonal antibody that targets B-cells, which play a key role in multiple sclerosis, and it is administered as a one-hour infusion twice a year after initial doses. This makes it different from other treatments like teriflunomide, which is taken orally and works through a different mechanism. ^{1 2 3 4 5}

Research Team

Daniel Harrison, MD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for people with relapsing multiple sclerosis (MS). Participants should either be starting treatment with ublituximab or currently on another MS medication. The study aims to enroll 30 patients, including both those beginning B-cell depletion therapy and a control group not changing their current stable MS treatments.

Inclusion Criteria

I am on a stable MS treatment with no change expected this year.

I am between 18 and 65 years old.

My doctor has recently referred me to start Ublituximab for MS.

Exclusion Criteria

I haven't had B-cell depleting therapy for MS in the last year.

I do not have eye diseases like diabetic retinopathy, macular degeneration, or glaucoma.

I have not used B-cell depleting therapy in the last year and don't plan to start it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ublituximab treatment and undergo specialized OCT scans at enrollment, Month 6, and Month 12

12 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ublituximab

Trial Overview The study is testing the effectiveness of ublituximab in altering MS pathology using new retinal imaging biomarkers detected by OCT scans. These biomarkers may indicate how well the body responds to treatment. Patients will undergo OCT scans at the start and two other times during the study.

Participant Groups

Group I: Other Disease Modifying Therapy Active Control 1 Intervention

People on stable doses of non-B-cell depleting multiple sclerosis disease modifying therapies will undergo the specialized OCT scan at baseline, 6 months, and 12 months.

Group II: Ublituximab Active Control 1 Intervention

Subjects recently prescribed ublituximab will undergo a specialized OCT at Enrollment, Month 6 and Month 12 as well as other neurologic assessments typically used in MS clinical trials such as EDSS, MSFC and SDMT

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

TG Therapeutics, Inc.

Industry Sponsor

Trials

41

Recruited

6,900+

Findings from Research

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 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, 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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Ublituximab: First Approval. [2023]

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

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

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

Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. [2022]

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

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