IMU-838 for Multiple Sclerosis

(ENSURE-2 Trial)

Recruiting at 108 trial locations

Overseen By Andreas Muehler, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Immunic AG

Must not be taking: Experimental drugs, MS treatments

Disqualifiers: Non-active MS, Neuromyelitis optica, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IMU-838 (Vidofludimus calcium) for individuals with relapsing multiple sclerosis (MS), a condition where the immune system mistakenly attacks the brain and spinal cord, causing symptoms like fatigue and vision problems. The trial aims to evaluate the treatment's effectiveness compared to a placebo (a pill with no active medicine) and to assess its safety. Participants should have relapsing MS and have experienced recent flare-ups or a specific type of MRI result in the past year. Those who meet these criteria and are interested in new treatment options might consider joining this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that IMU-838 is likely to be safe for humans?

Research has shown that IMU-838, also known as vidofludimus calcium, is generally well-tolerated. A previous study found it safe at doses ranging from 10 to 50 mg in healthy volunteers, indicating its safety. Another study confirmed that IMU-838 is safe for long-term use in people with relapsing-remitting multiple sclerosis.

Few reports of serious side effects have emerged, reassuring those considering this treatment. Overall, these findings suggest that IMU-838 is safe for humans, based on past studies and current data. So far, the evidence indicates it is a well-tolerated treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Unlike standard treatments for multiple sclerosis, which often include injectable therapies or medications that modulate the immune system, IMU-838 offers a new approach by targeting a specific enzyme called dihydroorotate dehydrogenase (DHODH). This mechanism helps reduce inflammation with potentially fewer side effects. Additionally, IMU-838 is taken orally once a day, offering a simpler and less invasive alternative to current treatments. Researchers are excited because this could mean more convenient and tolerable treatment options for patients managing multiple sclerosis.

What evidence suggests that IMU-838 might be an effective treatment for multiple sclerosis?

Research has shown that IMU-838, also known as vidofludimus calcium, may help treat multiple sclerosis (MS). In earlier studies, patients taking IMU-838 showed noticeable improvements in their disability over 24 weeks and experienced reduced fatigue, a common MS symptom. This treatment works by blocking an enzyme called DHODH, which plays a role in the immune system, potentially lowering inflammation in the nervous system. In this trial, participants will receive either IMU-838 or a placebo. Overall, these findings suggest that IMU-838 could be a useful option for managing symptoms in relapsing MS. ^{2 5 6 7 8}

Who Is on the Research Team?

Robert J. Fox, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IMU-838
• Placebo matching IMU-838 tablets

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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