Stwardnienie zanikowe boczne: badanie fazy III leku masitinib i AB1010

Kryteria wyłączenia kto nie może wziąć udziału (25)

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
2. Patient with pre-existing severe renal impairment, or with abnormal laboratory results from local laboratory assessments at screening: - Creatinine clearance < 60 mL/min (Cockcroft and Gault formula) - In case of proteinuria ≥1+ on the dipstick, proteinuria to creatininuria ratio will be assessed on urine sampled in the morning. If this ratio > 20 mg/mmol, the patient should be excluded.
3. Vulnerable population defined as: - Patients with a diagnosis of cancer within five years before screening except for basal cell carcinoma. - Patients with known diagnosis of human immunodeficiency virus (HIV) infection.
4. Patient with interstitial lung disease or pulmonary fibrosis.
5. Patient with active severe infection such as herpes, tuberculosis, viral hepatitis, human immunodeficiency virus infection
6. Patient with autoimmune conditions such as systemic lupus erythematosus
7. Patient with a diagnosis of cancer or evidence of continued disease within five years before screening
8. Patients with current or history of severe cardiovascular disease, assessed at screening - Ischemic heart disease (Myocardial infarction, unstable angina pectoris, acute coronary syndrome, coronary revascularization procedure)Congestive heart failure of NYHA Class III or IV - Stroke, including a transient ischemic attack, - Conduction disorders such as second degree or third-degree atrioventricular block not successfully treated with a pacemaker, Bi-fascicular block, uncontrolled atrial arrhythmia - Repolarization disorders such as QTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females, torsades de pointe, ventricular tachycardia - 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%
9. Patients, with two or more of the risk factors listed below assessed by a cardiologist 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 - Kidney disease, - Smoking (10 pack-year calculated as (packs smoked per day) × (years as a smoker), 20 cigarettes per pack)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. HeartScore is calculated for patients up to age 65. Patients older than this may be at a higher risk level than stated.
10. Patient who has been exposed to an investigational treatment within 3 months or five half-lives of the investigational product, whichever is longer, before the screening visit
11. Patient who has been treated to Edaravone within 30 days prior to screening
12. Patient with hypersensitivity to masitinib or its excipients and riluzole or its excipients
13. Patients treated concomitantly with Breast Cancer Resistance Protein (BCRP) substrates, inhibitors or inducers (e.g. anthracyclines, mitoxantrone, methotrexate, topotecan, irinotecan).
14. Subjects 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
15. Previous participation in an earlier study with masitinib
16. 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.
17. Patient under psychiatric, patient protected by law under guardianship or curatorship, patient in emergency situations, prisoners and patient without National health insurance
18. Patient with an FVC < 60% predicted normal value for gender, height, and age at screening
19. Patient with a weight < 41 kg and a BMI < 18 or > 35 kg/m² at screening or at baseline
20. Pregnant, or nursing female patient
21. Patient with history (or family history) of severe skin toxicities or reactions
22. 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
23. Patients 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 defined as: -Neutropenia with ANC <1.5 × 109/L - Anemia with Hgb <10 g/dl - Thrombocytopenia with platelet counts <150 × 109/L
24. Patient with history of hepatic disorders, with a known liver disease or recent alcohol abuse, or with abnormal laboratory results from local laboratory assessments defined as: - Hepatic transaminase levels > 2 ULN at baseline, or - Total bilirubin level > 1.5 ULN at baseline, or - Both hepatic transaminase levels and total bilirubin level outside of the normal ranges at screening and baseline, or - Albuminemia < 1 x LLN at screening and baseline, or - Patients with concomitant medication known to be associated with severe hepatotoxicity
25. Subjects who have received a live vaccine within 30 days prior to first IMP administration.