Masitinib for ALS

Recruiting at 66 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 if a new medication taken with riluzole can help ALS patients by reducing inflammation and protecting nerve cells. ALS patients are targeted because current treatments are not very effective.

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 masitinib safe for humans?

Masitinib has been tested in people with ALS and showed an acceptable safety profile, although some patients experienced side effects like those seen with placebo. Serious side effects were slightly more common with masitinib than with placebo, but no deaths were linked to the drug. ^{1 2 3 4 5}

How does the drug Masitinib for ALS differ from other treatments?

Masitinib is unique for ALS treatment because it is a tyrosine kinase inhibitor, which means it blocks certain enzymes that promote inflammation and cell growth, potentially slowing disease progression. This mechanism is different from Riluzole, the standard ALS treatment, which works by reducing damage to motor neurons. ^{6 7 8 9 10}

What data supports the effectiveness of the drug masitinib for ALS?

Research shows that masitinib, when added to the existing ALS drug riluzole, can slow the rate of functional decline in patients with ALS by 27% compared to a placebo. This suggests that masitinib may help improve the quality of life for ALS patients. ^{1 2 3 4 11}

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?

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

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. England pubmed.ncbi.nlm.nih.gov

Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Long-term survival analysis of masitinib in amyotrophic lateral sclerosis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment? [2022]

5. England pubmed.ncbi.nlm.nih.gov

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. [2021]

6. France pubmed.ncbi.nlm.nih.gov

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis]. [2013]

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

Synthesis, radiolabeling, and in vivo pharmacokinetic evaluation of the amyloid beta radioligand [11C]AZD4694 in nonhuman primates. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetic profiles of MGS0274 besylate (TS-134), a novel metabotropic glutamate 2/3 receptor agonist prodrug, in healthy subjects. [2021]

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

131I-IITM and 211At-AITM: Two Novel Small-Molecule Radiopharmaceuticals Targeting Oncoprotein Metabotropic Glutamate Receptor 1. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4. [2018]

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

Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2. [2023]