IMU-838 for Multiple Sclerosis

(ENSURE-2 Trial)

Recruiting in Palo Alto (17 mi)

+88 other locations

Overseen by Robert J. Fox, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Immunic AG

Must not be taking: Experimental drugs, MS treatments

Disqualifiers: Non-active MS, Neuromyelitis optica, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called IMU-838 to help adults with relapsing multiple sclerosis. The goal is to see if it can reduce the frequency and severity of their symptoms. The study will evaluate the effectiveness and safety of IMU-838.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that previous or current use of MS treatments and certain other medications may exclude you from participating. It's best to discuss your specific medications with the trial team.

Is IMU-838 (Vidofludimus calcium) safe for humans?

IMU-838 (Vidofludimus calcium) has been studied for safety in healthy male subjects and patients with conditions like rheumatoid arthritis and Crohn's disease. Some studies noted hematuria (blood in urine) at higher doses, which seemed related to the amount taken. Overall, it has been evaluated for safety in various conditions, including multiple sclerosis. ^{1 2 3 4 5}

How is the drug IMU-838 different from other multiple sclerosis treatments?

IMU-838 is unique because it selectively inhibits the enzyme dihydroorotate dehydrogenase (DHODH), which helps reduce brain lesions and disease activity in multiple sclerosis. This mechanism is different from other treatments, and it is taken orally, which can be more convenient for patients. ^{1 3 4 6 7}

Research Team

Robert J. Fox, MD

Principal Investigator

Mellen Center for MS, Neurological Institute, Cleveland Clinic, Ohio

Eligibility Criteria

Adults aged 18-55 with relapsing multiple sclerosis (RMS), including those with active secondary progressive MS, can join this trial. They must have had at least one or two relapses in the past year or two, respectively, or a recent MRI showing disease activity. People with non-active MS types, other similar diseases, kidney stones history, gout, uncontrolled autoimmune conditions besides type 1 diabetes and inflammatory bowel disease are excluded.

Inclusion Criteria

I am willing and able to follow the study's requirements.

I have had at least 2 flare-ups or a positive MRI in the last year.

Patients with an established diagnosis of MS according to 2017 McDonald Criteria

Exclusion Criteria

I haven't used any experimental drugs or joined any drug studies in the last 6 months, except for COVID-19 vaccines.

I have a significant medical or mental health condition.

I might have liver problems affecting my liver test results.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Main Treatment

Participants receive either IMU-838 or placebo for 72 weeks in a double-blind manner

72 weeks

Open Label Extension

Participants may opt into continuation of treatment with IMU-838 for up to 8 years

Up to 8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IMU-838 (Immunomodulator)
• Placebo matching IMU-838 tablets (Drug)

Trial Overview The ENSURE-2 study is testing the effectiveness of IMU-838 tablets compared to placebo pills in managing RMS. This large-scale phase 3 trial randomly assigns participants to either the medication group or placebo group without them knowing which they're receiving (double-blinded).

Participant Groups

Group I: IMU-838 Experimental Treatment 1 Intervention

IMU-838 (vidofludimus calcium), a small molecule inhibitor of DHODH. Formulation: Tablets with 15 or 30 mg IMU-838 for once daily oral intake in the morning.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo, as described for the test product, identical number of tablets as given for IMU-838.

Who Is Running the Clinical Trial?

Immunic AG

Lead Sponsor

Trials

8

Recruited

3,300+

Findings from Research

In a 24-week phase 2 trial involving patients with relapsing-remitting multiple sclerosis, vidofludimus calcium significantly reduced the number of new MRI brain lesions compared to placebo, indicating its efficacy in managing the disease.

The treatment was well tolerated, with no significant increase in serious adverse events or common side effects, suggesting a favorable safety profile for vidofludimus calcium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. Fox, RJ., Wiendl, H., Wolf, C., et al.[2022]

Vidofludimus (IMU-838) demonstrated good safety and tolerability in healthy male subjects across a wide dose range (10-50 mg) during two phase 1 studies, indicating it may be a safe option for treating conditions like rheumatoid arthritis and Crohn's disease.

The pharmacokinetics of IMU-838 were dose-proportional, with steady-state concentrations reached within 6-8 days, supporting its use as a once-daily oral medication without food affecting its absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects. Muehler, A., Kohlhof, H., Groeppel, M., et al.[2021]

The EDMUS database is a user-friendly system designed to collect and analyze data related to Multiple Sclerosis (MS), facilitating ongoing international multicenter trials.

Current studies using the EDMUS system include evaluations of treatment effects, such as the impact of pregnancy on MS and the effectiveness of early treatments with azathioprine and interferon-beta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EDMUS--a new European databank for multiple sclerosis. A brief introduction of ongoing and planned multicenter studies within the scope of the "European Concentrated Action for Multiple Sclerosis"]. Flachenecker, P., Hartung, HP.[2013]

Fingolimod is the first oral treatment approved for multiple sclerosis (MS) and its Phase III clinical trial data suggests a favorable benefit-risk profile compared to established MS therapies.

Long-term safety data and further studies are needed to make informed treatment decisions, emphasizing the importance of personalized medicine and patient involvement in the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis. Warnke, C., Stüve, O., Hartung, HP., et al.[2021]

In the CHAMPION-NMOSD study involving 58 adult patients with anti-aquaporin-4 antibody-positive NMOSD, ravulizumab demonstrated a 98.6% reduction in relapse risk compared to a placebo group from a previous trial, with no patients experiencing relapses during 84 patient-years of treatment.

The safety profile of ravulizumab was consistent with that of eculizumab, with most adverse events being mild to moderate, and no deaths reported, although two patients experienced recoverable meningococcal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Pittock, SJ., Barnett, M., Bennett, JL., et al.[2023]

References

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

A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A controlled, randomized phase II clinical trial for efficacy and safety evaluation of mannuronic acid in secondary progressive form of multiple sclerosis. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[EDMUS--a new European databank for multiple sclerosis. A brief introduction of ongoing and planned multicenter studies within the scope of the "European Concentrated Action for Multiple Sclerosis"]. [2013]

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

Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis. [2021]

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

Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. [2022]