5 Ongoing Clinical Trials Evaluating Treatment for MS

March 9 to March 15 marks multiple sclerosis (MS) awareness week for 2025, and it falls within National MS Education and Awareness Month. This education and awareness initiative had its inception in 2003, and it is the brainchild of MS Focus: the Multiple Sclerosis Foundation and affiliated groups.1

Multiple sclerosis is a chronic, central nervous system condition that many consider to be immune mediated, primarily affecting the brain, spinal cord, and optic nerves and inflicting permanent damage to the nerves’ protective covering, myelin.2-5 The exact cause of this progressive disease remains a mystery, and there is no cure; individuals are affected at varying levels.

Disease-modifying therapies encompass oral, self-injected, and infused medications, and the FDA has approved more than 20.6 Also, there are 28 ongoing clinical trials ongoing investigating BG00012, cladribine, fenebrutinib, fingolimod, ocrelizumab, ofatumumab, ozanimod, peginterferon beta-1a, tolebrutinib, and ublituximab, according to a search of active trials investigating treatments for MS on ClinicalTrials.gov on March 14.

To learn about 5 of these trials, please read on.

Disease-modifying therapies for MS encompass oral, self-injected, and infused medications, and the FDA has approved more than 20, with 28 clinical trials ongoing. | Image Credit: © arloo-stock.adobe.com

Tolebrutinib (NCT04742400)7

This Bruton tyrosine kinase (BTK) inhibitor is being investigated in a phase 2 trial for its ability to ameliorate chronically inflamed white matter MS-related brain lesions in adult patients on anti-CD20 therapy. The primary objective is the effectiveness of tolebrutinib 60 mg/day at 48 weeks, as measured via the disappearance of paramagnetic rim lesions. Secondary objectives are safety and tolerability of tolebrutinib 60 mg/day at 96 weeks, safety and tolerability of tolebrutinib 60 mg/day at 48 weeks plus 96 weeks at 120 mg/day, and repair of white matter lesions as gauged by modulated inflammation at the lesion edge. Long-term extension and follow-up are optional. The estimated completion date is December 31, 2025.

Fingolimod (NCT01892722)8

In this phase 3 trial, the safety and efficacy of daily administration of the sphingosine 1-phosphate receptor moderator fingolimod is being compared against interferon β-1a in pediatric patients aged 10 to 17 years. There is a 2-year double-blind, randomized, multicenter, active-controlled core phase and a 5-year extension phase. To be included, all patients had to have an official MS diagnosis and at least 1 MS relapse in the past year or 2 relapses in the past 2 years plus evidence of gadolinium-enhancing lesions on MRI with 6 months. Fingolimod is overall administered orally via weight-based dosing at 0.5 mg for patients weighing more than 40 kg and 0.25 mg for patients weighing 40 kg or less and interferon β-1a is given intramuscularly weekly. The estimated completion date is February 26, 2030.

Ocrelizumab (NCT04377555)9

Within this phase 4 open-label, prospective, single-arm, multicenter analysis, self-identified Black or African American and Hispanic/Latino patients with relapsing MS were enrolled who were either treatment-naïve or switching treatment after previous disease-modifying therapy with glatiramer acetate, diroximel fumarate, or dimethyl fumarate, among others. Ocrelizumab, a monoclonal antibody, is being administered via intravenous injection at 600 mg very 24 weeks, following a starter dose of two 300-mg infusions 14 days apart. Participants are followed for 1 year and can choose to enter the 1-year extension evaluation. A cerebrospinal fluid substudy includes a 2-year follow-up and 2 additional doses of 600-mg ocrelizumab at weeks 48 and 72. The estimated completion date is December 29, 2025.

Ublituximab (NCT04130997)10

Another monoclonal antibody, ublituximab is being evaluated for long-term safety and efficacy in adults patients who have relapsing MS. This phase 3 study is an open-label extension analysis of patients who completed 96 weeks of treatment in the ULTIMATE I (NCT03277261) or ULTIMATE II (NCT03277248) trials. Participants must agree to use medically acceptable contraception through 20 weeks after their final dose of the study drug. Treatment is administered via an initial 4-hour 150-mg infusion on day 1 and a 1-hour 450-mg infusion on day 15. Infusions that follow will be given for 1 hour every 24 weeks at 450 mg, and will continue from week 24 through week 312. The primary study outcome is annualized relapse rate, or total relapses divided by study treatment duration. The estimated completion date is February 1, 2030.

Fenebrutinib (NCT04544449)11

In the phase 3 FENtrepid trial, the efficacy and safety of the second BTK inhibitor on this list, oral fenbrutinib, are being evaluated among adult patients aged 18 to 65 years, except in Germany and Italy, where participants have be to aged 46 to 65 years. In the experimental arm, participants are randomized to receive the study drug or an intravenous ocrelizumab-matching placebo, and in the comparator arm, they are randomized to receive ocrelizumab or an oral fenbrutinib-matching placebo. The primary outcome of interest is time to onset of composite 12-week confirmed disability progression (CDP) over a minimum of 120 weeks, and secondary outcomes of interest include time to onset of composite 24-week CDP and percentage change in total brain volume via MRI. The estimated completion date is December 18, 2026.

References

1. National MS Education and Awareness Month. Multiple Sclerosis Foundation. Accessed March 14, 2025. https://msfocus.org/Get-Involved/MS-Awareness-Month

2. Multiple sclerosis. Johns Hopkins Medicine. Accessed March 14, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/multiple-sclerosis-ms

3. Mayo Clinic Staff. Multiple sclerosis. Mayo Clinic. Accessed March 14, 2025. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

4. Multiple sclerosis. Cleveland Clinic. Updated January 25, 2024. Accessed March 14, 2025. https://my.clevelandclinic.org/health/diseases/17248-multiple-sclerosis

5. Multiple sclerosis. National Institute of Neurological Disorders and Stroke. Updated January 31, 2025. Accessed March 14, 2025. https://www.ninds.nih.gov/health-information/disorders/multiple-sclerosis

6. Medications used off-label. National Multiple Sclerosis Society. Accessed March 14, 2025. https://www.nationalmssociety.org/managing-ms/treating-ms/disease-modifying-therapies/off-label-use

7. Tolebrutinib, a brain-penetrant Bruton's tyrosine kinase inhibitor, for the modulation of chronically inflamed white matter lesions in multiple sclerosis. ClinicalTrials.gov. Updated August 13, 2024. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT04742400

8. Safety and efficacy of fingolimod in pediatric patients with multiple sclerosis. ClinicalTrials.gov. Updated February 11, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT01892722

9. Prospective study to assess disease activity and biomarkers in minority participants with relapsing multiple sclerosis (RMS) after initiation and during treatment with ocrelizumab. ClinicalTrials.gov. Updated January 24, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT04377555

10. An extension study of ublituximab in participants with relapsing multiple sclerosis. ClinicalTrials.gov. Updated February 28, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT04130997

11. Study to evaluate the efficacy and safety of fenebrutinib compared with ocrelizumab in adult participants with primary progressive multiple sclerosis (FENtrepid). ClinicalTrials.gov. Updated January 27, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT04544449