A prospective, multicenter, randomised, double-blind, placebo-controlled, parallel groups, phase 3 Trial to compare the efficacy and safety of masitinib in combination with standard of care versus placebo in combination with standard of care in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ab Science

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-06-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AB Science

External identifiers

EU CT number

2024-511244-12-01

WHO UTN

U1111-1303-6775

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Efficacy

The objective of the trial is to evaluate the efficacy and safety of masitinib 4.5 mg/kg/day as add-on standard of care therapy in patients diagnosed with ALS

Secondary objectives 8

1. • PFS defined as the time from randomization to progression (decline of more than 9 points in ALSFRS-R score from baseline) or death
2. • Change in ALSAQ-40 from baseline to week 48
3. • Change in % of FVC from baseline to week 48
4. • Changes in upper- and lower-limb muscle strength using HHD from baseline to week 48
5. • Change in each component of clinician-rated CGI from baseline to week 48
6. • Change in CAFS from baseline to week 48 (outside of FDA)
7. • Overall survival (OS) defined as the time from randomization to the date of documented death
8. • Tracheostomy Free Survival (TFS) defined as time from randomization to the first occurrence of either death or tracheostomy.

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Patient, male or female, diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria [52] at screening
2. 10. At screening visit patient is able to understand, and willing to sign, and date the written informed consent form prior to any protocol-specific procedures. If patients are duly capable of trial consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to trial participation.
3. 11. At screening visit patient is able and willing to comply with trial protocol and to come on-site as per protocol visits schedule
4. 12. At screening visit patient is able to understand, and willing to follow the safety procedures mentioned on the patient card in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity
5. 2. Patient with a familial or sporadic ALS at screening
6. 3. Patient aged between 18 and 80 years old inclusive at screening
7. 4. Patient treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening visit and baseline visit
8. 5. Patient receiving or not Edaravone. If receiving Edaravone (oral suspension only), patients must have been taking it at stable dose for at least 30 days prior to screening visit
9. 6. Patient with onset of first symptom of ALS no longer than 36 months at screening
10. 7. Patient with a ALSFRS-R progression rate of > 0.3 and <1.1 point/month at screening visit i) as measured between onset of the disease and screening
11. 8. Patient with an ALSFRS-R total score at screening and baseline following rules below: - at least 3 on item #3 and - at least 2 on item #12 and - at least 1 on each of the other 10 items (i.e. item #1, #2, #4, #5a or #5b, #6, #7, #8, #9, #10, and #11)
12. 9. Contraception at screening and baseline: - Female patient of childbearing potential (entering the trial after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during the trial and for 8 months after the last treatment intake - Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during the trial and for 5 months after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the trial and for 5 months after the last treatment intake Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials. Highly effective and effective methods of contraception are detailed in appendix 16.1.
13. Patients who are not a candidate for QALSODY® Tofersen treatment

Exclusion criteria 21

1. 1. 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 at screening visit
2. 10. Patient with pre-existing severe renal impairment, or with abnormal laboratory results from local laboratory assessments at screening and baseline : - Creatinine clearance < 60 mL/min (Cockcroft and Gault formula) or - Proteinuria > 30 mg/dL (1+) on dipstick; in case of the proteinuria ≥ 1+ on the dipstick, 24 hours proteinuria must be > 1.5g/24 hours
3. 11. Patient with active tuberculosis infection, viral hepatitis, human immunodeficiency virus infection at screening
4. 12. Patient with a diagnosis of cancer or evidence of continued disease within five years before screening
5. 13. Patients with current or history of severe cardiovascular disease, assessed at screening - Myocardial infarction, - Unstable angina pectoris - Coronary revascularization procedure - Congestive heart failure of NYHA Class III or IV - Stroke, including a transient ischemic attack, - Second degree or third-degree atrioventricular block not successfully treated with a pacemaker, - Bi-fascicular block, - QTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females, - Drug induced heart failure or ischemic heart disease. - Radiotherapy induced cardiomyopathy. - Family history of unexpected death of cardiovascular origin. - Oedema of cardiac origin and left ventricular ejection fraction ≤ 50%
6. 14. Patients, with two or more of the risk factors listed below assessed, at screening, as Very High Risk (calculated SCORE ≥10%.) or High Risk calculated SCORE ≥5% and <10%) according to the Systematic Coronary Risk Estimation (SCORE): - Hypertension (uncontrolled) - Diabete - Chronic kidney disease - Current tabagism (≥ 10 Pack-year: equivalent to 1 pack of 20 cigarettes for 10 years with the formula N (number of packs of 20 cigarettes smoked daily) x T (number years smoking)) Patients who stopped smoking 6 months prior to the evaluation, are not concerned. - Hypercholesterolemia - COPD This assessment is done according to the Systematic Coronary Risk Estimation (SCORE) using the country specific free full version of HeartScore°, the interactive tool for predicting and managing the risk of heart attack and stroke in Europe, available at https://www.heartscore.org/en_GB/access If the country specific version is not available, EU one should be used.
7. 15. Patient treated concomitantly with substrates, inhibitors or inducers of BCRP at screening and baseline
8. 16. Participants with a significant pulmonary disorder not attributed to ALS or who require treatments that might complicate the evaluation of the effect of ALS on respiratory function at screening visit
9. 17. Previous treatments with masitinib
10. 18. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the trial, poses any added risk for the patient, or confounds the assessment of the patient at screening visit
11. 19. Patient under psychiatric care, patient protected by law under guardianship or curatorship, patient in emergency situations, prisoners and patient without National health insurance at screening visit
12. 2. Patient with hypersensitivity to masitinib excipients or riluzole at screening visit
13. 3. Patient with an FVC < 70%, predicted normal value for gender, height, and age, at screening and baseline
14. 4. Patient with a weight < 41 kg and a BMI < 18 or > 35 kg/m² at screening and baseline visit
15. 5. Pregnant, or nursing female patient at screening and baseline
16. 6. Patient with history (or family history) of severe skin toxicities or reactions at screening
17. 7. Patients treated by drugs known to be at high risk for Stevens-Johnson Syndrome or for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome at screening and baseline
18. 8. Patient with history of severe bone marrow disorders such as agranulocytosis or aplasia, or with abnormal laboratory results from local laboratory assessments at screening and baseline: - Neutropenia with ANC < 1.5x109/L, or - Anemia with Hgb < LLN or red blood cell count below the LLN, or - Thrombocytopenia with platelets counts < 150 x 109/L
19. 9. Patient with history of hepatic disorders, with a known liver disease or recent alcohol abuse, or with abnormal laboratory results from local laboratory assessments, at screening and baseline, defined as: - Hepatic transaminase levels > 2 ULN, or - Total bilirubin level > 1.5 ULN, or - Both hepatic transaminase levels and total bilirubin level outside of the normal ranges, or - Albuminemia < 1 x LLN - Patients with concomitant medication known to be associated with severe hepatotoxicity
20. Patients who have received a live vaccine within 30 days before the first administration of the investigational medicinal product
21. Patient with interstitial lung disease or pulmonary fibrosis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary analysis will be done in the ITT population. Absolute change from baseline at week 48 in ALSFRS-R score will be analysed using multiple imputation model.

Secondary endpoints 11

1. • PFS analysed using the log rank test. Kaplan-Meier Plots
2. • ALSAQ-40 change analyzed using the same model as primary
3. • FVC change from baseline analysed using the same model as primary
4. • Upper- and lower-limb muscle strength using HHD summarized by treatment arm
5. • Clinician-rated CGI summarized by treatment arm
6. • CAFS analysed using the Generalised GehanWilcoxon rank test
7. • OS analysed using the log rank test. Kaplan-Meier Plots
8. • TFS analysed using the Gehan-Wilcoxon test and the log rank test. Kaplan-Meier Plots
9. • Safety: Occurrence of Adverse Events (AE), changes on physical examination, vital signs (blood pressure, heart rate, weight and temperature), ECG and clinical laboratory tests (haematology, biochemistry, urinalysis, urinary cytology)
10. • Identification of pharmacodynamic biomarker(s)
11. • Measurement of pharmacokinetic parameters of Masitinib

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ab Science

Sponsor organisation

Ab Science

Address

3 Avenue George V

City

Paris

Postcode

75008

Country

France

Scientific contact point

Organisation

Ab Science

Contact name

Shruti Chatterjee

Public contact point

Organisation

Ab Science

Contact name

Shruti Chatterjee

Third parties 2

Locations

6 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 5 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications