What is the mechanism of action of this treatment?

The most common treatments for Multiple Sclerosis (MS) include disease-modifying therapies (DMTs) that target various aspects of the immune system to reduce inflammation and neurodegeneration. For example, teriflunomide, similar to IMU-838, selectively inhibits dihydroorotate dehydrogenase (DHODH), reducing the proliferation of activated T and B lymphocytes, which are key players in the autoimmune response in MS. Other treatments like interferon beta-1a modulate the immune response and reduce inflammatory activity, while dimethyl fumarate activates the Nrf2 pathway, providing neuroprotection and anti-inflammatory effects. These mechanisms are crucial for MS patients as they help to slow disease progression, reduce relapse rates, and manage symptoms, thereby improving quality of life.

What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis that involve selective inhibition of dihydroorotate dehydrogenase (DHODH), such as teriflunomide, often have side effects including liver enzyme elevations, gastrointestinal issues (nausea, diarrhea), hair thinning, and increased risk of infections. Other disease-modifying therapies (DMTs) for MS, like interferon beta and fingolimod, can cause flu-like symptoms, injection site reactions, elevated liver enzymes, and more serious risks like bradyarrhythmia, macular edema, and increased susceptibility to infections. Patients should discuss these potential side effects with their healthcare provider to make an informed decision.

What prior FDA approvals exist?

One notable FDA-approved drug for Multiple Sclerosis that works similarly to IMU-838 is teriflunomide (Aubagio). Teriflunomide also inhibits dihydroorotate dehydrogenase (DHODH), thereby reducing the proliferation of activated T and B lymphocytes, which are implicated in the autoimmune response in MS. This mechanism helps to modulate the immune system and reduce the frequency of MS relapses. Other treatments for MS include interferon beta-1a and beta-1b, glatiramer acetate, and dimethyl fumarate, which work through different mechanisms to reduce inflammation and modulate the immune response.

What other types of research exist?

Promising novel alternatives to IMU-838 for Multiple Sclerosis patients in 2024 include: 1. BTK inhibitors (e.g., tolebrutinib) which target B-cell signaling pathways. 2. Anti-CD20 monoclonal antibodies (e.g., ublituximab) that deplete B-cells. 3. S1P receptor modulators (e.g., ponesimod) which reduce lymphocyte egress from lymph nodes. 4. Cladribine, a purine analog that targets lymphocyte reduction. These treatments offer different mechanisms of action and have shown efficacy in clinical trials.

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Immunomodulator

IMU-838 for Progressive Multiple Sclerosis (CALLIPER Trial)

Phase 2

Waitlist Available

Led By R. F., MD

Research Sponsored by Immunic AG

Eligibility Criteria Checklist

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

Must have

No evidence of relapse in the last 24 months before randomization, AND Patients diagnosed according to 2017 revised McDonald Criteria 1 and the 2013 revised classification of disease courses 2 as either

No evidence of relapse in the last 24 months before randomization

Must not have

Any disease other than MS that may better explain the signs and symptoms, including a history of complete transverse myelitis

Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-associated encephalomyelitis (i.e.,presence of anti-NMO [aquaporin-4] antibodies or anti-MOG antibodies)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 120 weeks

Summary

This trial is testing a new medication called IMU-838 to help adults with Progressive Multiple Sclerosis. The medication aims to reduce inflammation and slow down the worsening of the disease. The study will check if the medication is safe and effective over a long period.

Who is the study for?

Adults aged 18-65 with Progressive Multiple Sclerosis (SPMS or PPMS) who haven't had a relapse in the last 24 months. They must have an EDSS score of 3.0 to 6.5, show disability progression not related to relapses, and be able to follow the study protocol. Excluded are those with other possible causes for symptoms, previous MS treatments within certain timeframes, recent SARS-CoV-2 infection without negative tests, positive tests for TB or hepatitis B/C/HIV, use of investigational products recently, or signs of NMO/MOG-associated encephalomyelitis.

What is being tested?

The CALLIPER trial is testing IMU-838's effectiveness and safety against a placebo in managing Progressive Multiple Sclerosis. Participants will be randomly assigned to either receive IMU-838 or a matching placebo in this double-blind study where neither they nor the researchers know who gets which treatment.

What are the potential side effects?

While specific side effects for IMU-838 aren't listed here, common drug-related side effects could include gastrointestinal issues like nausea and diarrhea; liver function changes; potential risk of infections due to immune system impact; fatigue; headache; and allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

Select...

I haven't had a relapse in 2 years and my diagnosis follows specific criteria.

Select...

My condition has not worsened in the last 2 years.

Select...

I have been diagnosed with SPMS or PPMS according to the latest criteria.

Select...

I am between 18 and 65 years old.

Select...

I am between 18 and 65 years old.

Exclusion Criteria

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

Select...

My symptoms are not caused by conditions other than MS.

Select...

I have signs or test results indicating NMO or MOG-associated encephalomyelitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 120 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~120 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 120 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

Efficacy of IMU-838 versus placebo

Secondary study objectives

Efficacy of IMU-838 versus placebo in terms of disability worsening

Other study objectives

Safety IMU-838 versus placebo

Side effects data

From 2021 Phase 2 & 3 trial • 234 Patients • NCT04379271

21%

Hypertriglyceridaemia

Glycosylated haemoglobin increased

Headache

Haematuria

Tachycardia

Sinus bradycardia

Hypertensive crisis

Hyperglycaemia

Alanine aminotransferase increased

Hypertension

Anaemia

Bradycardia

Hepatocellular injury

Death

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

IMU-838

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: IMU-838Experimental Treatment1 Intervention

IMU-838 as tablet; Administration: Oral - daily

Group II: PlaceboPlacebo Group1 Intervention

Matching placebo as tablet; Administration: Oral - daily

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

IMU-838

2020

Completed Phase 3

~280

0 / 7Eligibility 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) include disease-modifying therapies (DMTs) that target various aspects of the immune system to reduce inflammation and neurodegeneration. For example, teriflunomide, similar to IMU-838, selectively inhibits dihydroorotate dehydrogenase (DHODH), reducing the proliferation of activated T and B lymphocytes, which are key players in the autoimmune response in MS. Other treatments like interferon beta-1a modulate the immune response and reduce inflammatory activity, while dimethyl fumarate activates the Nrf2 pathway, providing neuroprotection and anti-inflammatory effects. These mechanisms are crucial for MS patients as they help to slow disease progression, reduce relapse rates, and manage symptoms, thereby improving quality of life.

Teriflunomide Treatment of Multiple Sclerosis Selectively Modulates CD8 Memory T Cells.Disease-modifying treatments for progressive multiple sclerosis.Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study.