IMU-838 for Multiple Sclerosis

(ENSURE-1 Trial)

Recruiting at 84 trial locations

Overseen By Olena Portianka

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Immunic AG

Must not be taking: Experimental drugs, MS treatments

Disqualifiers: Non-active MS, NMO, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1050 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing IMU-838, a medication for adults with relapsing multiple sclerosis. The drug aims to reduce immune system activity to prevent nerve damage and manage symptom flare-ups.

Will I have to stop taking my current medications?

The trial 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. ^{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 2 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 relapsing-remitting MS and active secondary progressive MS, who've had at least one recent flare-up or positive MRI scan. Participants must be able to follow the study plan and not have other autoimmune diseases, conditions that mimic MS symptoms, certain infections, liver issues, gout, major illnesses affecting study participation or a history of kidney stones.

Inclusion Criteria

I have been diagnosed with MS according to the 2017 McDonald Criteria.

I have relapsing-remitting MS or active secondary progressive MS.

Written informed consent given prior to any study-related procedure.

Exclusion Criteria

I have signs or test results indicating NMO or MOG-IgG disease.

My symptoms are not caused by conditions other than MS.

I have not had a long-term infection in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Main Treatment

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

72 weeks

Open Label Extension

Participants may continue to receive 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
• Placebo matching IMU-838 tablets

Trial Overview The trial is testing IMU-838 tablets against placebo pills in people with RMS to see if they're effective and safe. It's a large-scale Phase 3 study where participants are randomly assigned to either the medication or placebo group without knowing which one they receive (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

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]

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]

In a 6-month phase II trial involving patients with secondary progressive multiple sclerosis, the novel immunosuppressive drug β-D-Mannuronic acid (M2000) showed a significant reduction in disability progression compared to conventional treatments, with a notable decrease in the Expanded Disability Status Scale (EDSS) score (p < 0.009).

M2000 demonstrated better performance in MRI-related measurements compared to conventional drugs, and importantly, no short-term side effects were observed, indicating its potential safety and efficacy as a treatment option for MS.

NCBI (Pubmed)

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. Najafi, S., Moghadam, NB., Saadat, P., et al.[2022]

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]

Teriflunomide, an oral treatment for relapsing-remitting multiple sclerosis, has shown consistent efficacy in clinical trials, with safety data pooled from over 3044 patients and a treatment duration exceeding 12 years.

The safety profile of teriflunomide is manageable, with common side effects including ALT increase, headache, diarrhea, hair thinning, and nausea, mostly mild-to-moderate in intensity, and no new safety concerns identified in long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. Comi, G., Freedman, MS., Kappos, L., et al.[2022]

References

1. 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]

2. 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]

3. 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]

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]