IMU-838 for Multiple Sclerosis

(ENSURE-1 Trial)

Recruiting in Palo Alto (17 mi)

+84 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, NMO, others

Pivotal Trial (Near Approval)

Prior Safety Data

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}

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.

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

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Collier Neurologic Specialists Naples, FL

Consultants in Neurology, Ltd Northbrook, IL

Neurology Associates of Ormond Beach Ormond Beach, FL

Xenoscience, Inc., 21st Century Neurology Phoenix, AZ

More Trial Locations

Who Is Running the Clinical Trial?

Immunic AG Lead Sponsor

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] Vidofludimus is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). The clinical efficacy and safety profile of vidofludimus has been analyzed in patients suffering from rheumatoid arthritis and Crohn's disease and ulcerative colitis. In previous sudies, hematuria at higher doses occurred in close temporal relationship to vidofludimus administration and appeared to be dose related. The present report describes the results from two phase 1 studies conducted in healthy male subjects to investigate the safety, tolerability and pharmacokinetics after single and multiple ascending (SAD and MAD) oral doses of IMU-838 (vidofludimus calcium, tablets containing a specific polymorph). The effect of food on the pharmacokinetics of IMU-838 was also assessed in the SAD study.

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] Inhibition of dihydroorotate dehydrogenase suppresses magnetic resonance imaging brain lesions and disease activity in multiple sclerosis but has limiting tolerability. We assessed the safety and efficacy of vidofludimus calcium, a novel, selective dihydroorotate dehydrogenase inhibitor, in patients with relapsing-remitting multiple sclerosis.

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] The β-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has shown positive effects in experimental model of multiple sclerosis (MS). In this study, our aim was to assess efficacy and safety outcomes in MS treated patients with mannuronic acid compared to the conventional drug.

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] EDMUS, the European Database for Multiple Sclerosis (MS), was established on the occasion of the first European Concerted Action for MS under the auspices of the European Community. The system is user-friendly and makes it possible to record and retrieve data relevant to MS. Within the framework of another European Concerted Action, several international multicenter trials are currently in progress. EVALUED, a validation of the EDMUS system, assesses the interrater variability; PRIMS examines the influence of pregnancy and the post-partum period on the course of MS; and PRESTIMUS investigates predictive factors in suspected MS. Further, planned studies include ERAZMUS (early azathioprine and interferon-beta treatment in MS) and AZASTOP, which is designed to evaluate the effect of stopping azathioprine treatment.

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

Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis. [2021] This review summarizes Phase III clinical trial data available for fingolimod. The main purpose is to evaluate the benefit-risk profile of fingolimod, the first oral compound available for treatment of multiple sclerosis (MS) and just recently approved by the European authorities. The authors place this evaluation in the context of the known safety and efficacy profile of established compounds for therapy of MS to outline the current and future potential of fingolimod. The authors conclude that only long-term safety data from post-marketing surveillance plans, together with additional head-to-head studies, would allow evidence-based treatment decisions. Furthermore, risk-profile analyses including patient history, exposure data to certain pathogens, and genetic analyses may potentially help to choose the right drug for individual patients in the future. Until these approaches toward an individualized medicine have been validated, treatment decisions for one or the other compound will have to be based partly on class IV evidence. Therefore, a close dialog with the well-informed patient, secured by effective risk mitigation plans, is required to choose the compound.

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

Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. [2023] CHAMPION-NMOSD (NCT04201262) is a phase 3, open-label, externally controlled interventional study evaluating the efficacy and safety of the terminal complement inhibitor ravulizumab in adult patients with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab binds the same complement component 5 epitope as the approved therapeutic eculizumab but has a longer half-life, enabling an extended dosing interval (8 vs 2 weeks).

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

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. [2022] Teriflunomide, a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis, has demonstrated consistent efficacy on clinical and MRI parameters in clinical trials.