Masitinib for ALS

Recruiting at 79 trial locations

Overseen By Clinical Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AB Science

Must be taking: Riluzole

Disqualifiers: Dementia, Uncontrolled diseases, FVC < 60%, 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

Duration: 48 weeks

495 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with Amyotrophic Lateral Sclerosis (ALS), a condition affecting nerve cells in the brain and spinal cord. Researchers compare the effectiveness and safety of masitinib (a type of tyrosine kinase inhibitor) combined with riluzole against a placebo (a substance with no therapeutic effect) also combined with riluzole. Participants may receive different doses of masitinib to determine the most effective one. The trial seeks individuals diagnosed with ALS within the last two years, who are already taking riluzole, and have experienced a certain rate of progression in their condition. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Do I have to stop taking my current medications for the trial?

The trial requires participants to be on a stable dose of riluzole (100 mg/day) for at least 12 weeks before starting. The protocol does not specify if you need to stop other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that masitinib, when combined with riluzole, is generally well-tolerated by people with ALS. Studies have found that taking masitinib at a dose of 4.5 mg per kilogram of body weight daily can slow the loss of muscle function. Starting treatment before the disease becomes too severe may also extend life expectancy.

Safety checks occur at each step when increasing the dose to manage any side effects effectively. These studies have not identified any serious new safety concerns, indicating that most people can tolerate the treatment without major issues. However, like any treatment, some individuals might experience side effects. Discussing these with the medical team conducting the trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Masitinib is unique because it targets the immune system's role in ALS, unlike current treatments that mainly focus on slowing nerve damage. This drug specifically inhibits certain enzymes called tyrosine kinases, which may help reduce inflammation and slow disease progression. Researchers are excited about masitinib because it could offer a new way to manage ALS symptoms and potentially improve patient outcomes beyond what existing options, like riluzole and edaravone, can achieve.

What evidence suggests that this trial's treatments could be effective for ALS?

Research has shown that masitinib, when combined with riluzole, may help treat Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will receive either masitinib at a dose of 4.5 mg/kg/day or 6.0 mg/kg/day, both in combination with riluzole, or a placebo with riluzole. In earlier studies, patients taking masitinib (4.5 mg per kilogram of body weight each day) lived more than two years longer on average and had a 47% lower risk of death compared to those not taking it. Additionally, masitinib slowed the decline in physical abilities by 27% and improved quality of life by 29% over 48 weeks. These results suggest that masitinib could be a helpful additional treatment for ALS, offering hope in slowing the disease's progression. ^{2 4 5 6 7}

Who Is on the Research Team?

Albert Ludolph, MD, PhD

Principal Investigator

Department of Neurology, University of Ulm, Germany

Are You a Good Fit for This Trial?

This trial is for ALS patients diagnosed within the last 24 months, who have been on a stable dose of riluzole. They must show disease progression and have certain scores on the ALSFRS-R scale. Excluded are those with dementia, other serious diseases, pregnant or nursing women, or with low lung function.

Inclusion Criteria

You have been diagnosed with ALS for no more than 24 months.

You have been taking the same dose of riluzole (100 mg/day) for at least 12 weeks before the study starts.

You have been diagnosed with ALS using specific criteria from the World Federation of Neurology.

Exclusion Criteria

Patient with dementia or significant neurological, psychiatric, systemic or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results

Pregnant, or nursing female patient

Your lung function is less than 60% of what is expected for someone of your gender, height, and age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive masitinib or placebo in combination with riluzole, with dose escalation for masitinib over 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are assessed for progression-free survival up to 36 months

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Masitinib
• Placebo
• Riluzole

Trial Overview The study tests masitinib's effectiveness and safety in combination with riluzole compared to a placebo plus riluzole in treating ALS. Participants will either receive masitinib at different doses or a placebo alongside their regular riluzole treatment.

How Is the Trial Designed?

Group I: Masitinib (6.0) & Riluzole Experimental Treatment 2 Interventions

Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d.

Group II: Masitinib (4.5) & Riluzole Experimental Treatment 2 Interventions

Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d

Group III: Placebo & Riluzole Placebo Group 2 Interventions

Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.

Masitinib is already approved in European Union, United States for the following indications:

Approved in European Union as Masivet for:

• Mast cell tumors in dogs

Approved in United States as Kinavet for:

• Mast cell tumors in dogs

Who Is Running the Clinical Trial?

AB Science

Lead Sponsor

Trials

39

Recruited

15,700+

Published Research Related to This Trial

MN-166 (ibudilast) shows promise as a neuroprotective treatment for ALS by inhibiting inflammation and glial cell activation, with early studies indicating potential improvements in survival and disease progression.

The ongoing COMBAT-ALS study, involving a randomized, double-blind, placebo-controlled design, aims to rigorously evaluate the safety, tolerability, and efficacy of MN-166 on various outcomes in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. Oskarsson, B., Maragakis, N., Bedlack, RS., et al.[2022]

Riluzole is currently the only approved treatment for ALS, but its efficacy is mild, and despite extensive research, most clinical trials for new ALS treatments have not shown significant benefits.

Recent studies on oral masitinib and intravenous edaravone suggest they may be promising new therapies for ALS, with masitinib including a broader patient population in its trials compared to edaravone, which could impact their future use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment? Petrov, D., Mansfield, C., Moussy, A., et al.[2022]

In a study of 153 ALS patients, riluzole was found to have an acceptable safety profile, with 50.3% experiencing adverse effects, primarily gastrointestinal issues, hepatotoxicity, and fatigue.

Riluzole's mechanism of action suggests it may also be beneficial for other neurodegenerative diseases related to glutamate excitotoxicity, warranting further investigation and monitoring for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis]. Roch-Torreilles, I., Camu, W., Hillaire-Buys, D.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8388186/

Long-term survival analysis of masitinib in amyotrophic lateral ... Notably, a statistically significant survival benefit of over 2 years and 47% reduced risk of death for patients receiving masitinib (4.5 mg/kg/day) as compared ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03127267

Efficacy and Safety of Masitinib Versus Placebo in ... The objective is to compare the efficacy and safety of masitinib in combination with riluzole versus matched placebo in combination with riluzole for the ...

3. ab-science.com ab-science.com/masitinib-in-neurology/

Masitinib in Neurology - AB Science 27% slowing of ALSFRS-R deterioration at week 48 (primary analysis) · 29% slowing of deterioration in quality-of-life (ALSAQ-40) · 22% slowing of deterioration in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S075333222300166X

Masitinib: The promising actor in the next season of ... Masitinib can increase overall survival and slow ALSFRS-R deterioration. Abstract. Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high ...

5. ema.europa.eu ema.europa.eu/en/documents/assessment-report/masitinib-ab-science-epar-refusal-public-assessment-report_en.pdf

Masitinib AB Science | EMA the efficacy and safety of masitinib as add-on therapy in Amyotrophic Lateral Sclerosis (ALS) patients treated with Riluzole. Patients will ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34457038/

Long-term survival analysis of masitinib in amyotrophic ... Oral masitinib (4.5 mg/kg/day) could prolong survival by over 2 years as compared with placebo, provided that treatment starts prior to severe impairment of ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000203460

Masitinib Shows Prolonged Survival in Amyotrophic Lateral ... Masitinib (4.5 mg/kg/d), administered orally as an add-on to standard riluzole over 48 weeks, slowed the rate of functional decline in ALS patients.