Clemastine Fumarate for Multiple Sclerosis

(ReVIVE Trial)

Overseen By Angelica Montevirgen

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: Corticosteroids, Alemtuzumab, Mitoxantrone, others

Disqualifiers: Brain atrophy, Cardiac block, Cancer, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

74 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Clemastine Fumarate to see if it can repair myelin in patients with relapsing-remitting multiple sclerosis who have chronic brain lesions. The medication helps immature brain cells develop into myelin-producing cells, potentially fixing the damage caused by MS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any other remyelinating therapy or have been treated with certain medications like corticosteroids within 30 days before the trial. It's best to discuss your current medications with the trial team to see if they might affect your participation.

How is the drug Clemastine Fumarate different from other multiple sclerosis treatments?

Clemastine Fumarate is unique because it is primarily an antihistamine used for allergies, but it is being explored for multiple sclerosis due to its potential to promote myelin repair (restoration of the protective covering of nerves), which is not a focus of most existing MS treatments. ^{1 2 3 4 5}

Research Team

Ari J Green, MD, MCR

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults aged 18-55 with relapsing-remitting multiple sclerosis (MS) diagnosed within the last 15 years. Participants must use effective birth control and provide informed consent. Excluded are those with recent MS lesions, hypersensitivity to clemastine, steroid treatment within 30 days, cancer history, suicidal behavior in past 6 months, pregnancy or breastfeeding intentions, other concurrent study involvement without approval.

Inclusion Criteria

- Not heterosexually active (patients who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study)

I am between 18 and 55 years old.

I have relapsing-remitting MS diagnosed within the last 15 years.

Exclusion Criteria

I have a history of serious heart rhythm problems.

You have had issues with drugs or alcohol in the past year.

I have not taken corticosteroids in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Clemastine Fumarate or placebo for 90 days, followed by a switch to the alternate treatment for another 90 days

6 months

Baseline, 3-month, and 6-month visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Clemastine Fumarate

Trial Overview The trial tests Clemastine Fumarate as a potential myelin repair therapy against a placebo in MS patients. It measures changes using multi-parametric MRI and a new technique called Ultrashort Echo Time (UTE) MRI to assess remyelination of chronic brain lesions.

Participant Groups

Group I: Placebo, then Clemastine 8 mg Experimental Treatment 2 Interventions

Group 2 will receive the placebo (a sugar pill) for the first 90 days and then switch to the treatment (clemastine 8mg/day) for the remaining 90 days

Group II: Clemastine 8 mg, then Placebo Experimental Treatment 2 Interventions

Group 1 will receive the treatment (clemastine 8mg/day) for the first 90 days and then switch to the placebo (a sugar pill) for the remaining 90 days

Clemastine Fumarate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Approved in European Union as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Approved in Canada as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Dimethyl fumarate has been shown to significantly reduce relapse rates in patients with relapsing-remitting multiple sclerosis (MS), with a reduction of 34% to 49% in the proportion of patients experiencing relapses over two years, based on two phase III trials (DEFINE and CONFIRM).

The safety profile of dimethyl fumarate is comparable to placebo, with serious adverse effects occurring at similar rates; however, some patients experienced intolerable flushing and gastrointestinal issues, leading to discontinuation in 3% and 4% of cases, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. Venci, JV., Gandhi, MA.[2015]

In a study of patients with multiple sclerosis, dimethyl fumarate (DMF) treatment led to a significant decrease in CD4(+) and CD8(+) memory T cells, suggesting a targeted effect on these immune cells.

DMF treatment also resulted in a shift in T helper cell populations, increasing anti-inflammatory TH2 cells while decreasing pro-inflammatory TH1 cells, which may benefit patients with TH1-driven disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis. Gross, CC., Schulte-Mecklenbeck, A., Klinsing, S., et al.[2022]

In a study of 735 patients with relapsing-remitting multiple sclerosis, dimethyl-fumarate (DMF) reduced the annual relapse rate by 63.2%, with 85% of patients relapse-free at 12 months.

DMF was found to be safe, with the most common side effects being flushing (37.2%) and gastro-enteric issues (31.1%), and it showed significant benefits for both treatment-naïve patients and those switching from other therapies due to tolerability or efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. Mallucci, G., Annovazzi, P., Miante, S., et al.[2018]

Dimethyl-fumarate, an approved treatment for relapsing-remitting Multiple Sclerosis, was well-tolerated by a 55-year-old woman, with the only notable side effect being moderate flushing.

Although transient hair loss was not previously reported as a side effect of dimethyl-fumarate, it was observed in this patient after starting the therapy, but it resolved after two months, suggesting a possible link to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis. Losavio, FA., Lucchini, M., De Fino, C., et al.[2017]

In a study of 2113 patients with relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate and fingolimod were found to have similar effectiveness in reducing relapse rates and preventing disability worsening, with no significant differences in outcomes.

Both treatments showed comparable results for both treatment-naïve patients and those switching from other disease-modifying therapies, indicating that either medication can be a viable first-line option for managing RRMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of dimethyl fumarate and fingolimod in relapsing-remitting multiple sclerosis. Lorscheider, J., Benkert, P., Lienert, C., et al.[2021]

References

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

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. [2015]

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

Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparative analysis of dimethyl fumarate and fingolimod in relapsing-remitting multiple sclerosis. [2021]