What is the mechanism of action of this treatment?

The most common treatments for Multiple Sclerosis (MS) primarily aim to modulate the immune system to reduce inflammation and prevent neurodegeneration. IMU-838, for example, inhibits dihydroorotate dehydrogenase, which reduces the proliferation of activated T and B cells, thereby limiting the immune response that damages myelin. Other treatments, such as interferon beta and glatiramer acetate, work by modulating the immune response to decrease the frequency and severity of relapses. These mechanisms are crucial for MS patients as they help to slow disease progression, reduce the accumulation of disability, and improve overall quality of life.

What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis that inhibit dihydroorotate dehydrogenase, such as teriflunomide, have known side effects including liver toxicity, gastrointestinal issues (nausea, diarrhea), hair thinning, and increased risk of infections. Other disease-modifying therapies (DMTs) for MS, like interferon beta and glatiramer acetate, can cause flu-like symptoms, injection site reactions, and potential liver enzyme elevations. Fingolimod, another DMT, is associated with bradyarrhythmia, macular edema, and increased susceptibility to infections. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

Several drugs have been FDA-approved for the treatment of Multiple Sclerosis (MS) that share a similar mechanism to IMU-838, which inhibits dihydroorotate dehydrogenase. One such drug is teriflunomide, which also targets dihydroorotate dehydrogenase to reduce the proliferation of activated T and B cells. Other FDA-approved treatments for MS include interferon beta-1a and beta-1b, glatiramer acetate, dimethyl fumarate, and monoclonal antibodies like natalizumab and ocrelizumab. These treatments work through various mechanisms to modulate the immune system and reduce disease activity.

What other types of research exist?

Promising novel alternatives to IMU-838 for Multiple Sclerosis patients include: 1) Hematopoietic Stem Cell Transplantation (HSCT), which has shown significant benefits in reducing disease progression and relapse rates in patients with refractory MS. 2) Dimethyl fumarate (BG-12), which has demonstrated efficacy in reducing relapse rates and new brain lesions in clinical trials. 3) Monoclonal antibody therapies such as ocrelizumab and alemtuzumab, which target B cells and have shown effectiveness in reducing disease activity and progression.

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Immunomodulator

IMU-838 for Multiple Sclerosis (ENSURE-2 Trial)

Phase 3

Recruiting

Led By Robert J. Fox, MD

Research Sponsored by Immunic AG

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Active disease as defined by Lublin 2014 evidenced prior to Screening by: At least 2 relapses in the last 24 months before randomization, or At least 1 relapse in the last 12 months before randomization, or A positive Gd+ MRI scan (brain and/or spine) in the last 12 months prior to randomization

Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014

Must not have

Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease)

History or presence of any major medical or psychiatric illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 72 weeks

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

While specific side effects for IMU-838 aren't listed here, common risks may include gastrointestinal issues like nausea and diarrhea; potential liver function changes; risk of infection due to immune system impact; and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have relapsing-remitting or active secondary progressive MS.

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I am between 18 and 55 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any active and uncontrolled autoimmune diseases except possibly MS, type 1 diabetes, or inflammatory bowel disease.

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I have a significant medical or mental health condition.

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My MS is in a non-active, progressive stage.

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My symptoms are not caused by conditions other than MS.

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I have been diagnosed with gout.

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

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I have a history of kidney stones or a condition that often causes them.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 72 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~72 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 72 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To evaluate efficacy of IMU-838 versus placebo based on time to first relapse

Secondary study objectives

Effect of IMU-838 versus placebo on cognitive performance

Effect of IMU-838 versus placebo on disability progression

Effect of IMU-838 versus placebo on volume of new T2 lesions

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: IMU-838Experimental Treatment1 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: PlaceboPlacebo Group1 Intervention

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

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Multiple Sclerosis (MS) primarily aim to modulate the immune system to reduce inflammation and prevent neurodegeneration. IMU-838, for example, inhibits dihydroorotate dehydrogenase, which reduces the proliferation of activated T and B cells, thereby limiting the immune response that damages myelin. Other treatments, such as interferon beta and glatiramer acetate, work by modulating the immune response to decrease the frequency and severity of relapses. These mechanisms are crucial for MS patients as they help to slow disease progression, reduce the accumulation of disability, and improve overall quality of life.

Disease-modifying treatments for progressive multiple sclerosis.