A prospective, multicenter, randomised, double-blind, placebo-controlled, parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with Riluzole versus placebo in combination with Riluzole in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- ALSamyotrophic lateral sclerosis10029317
- Registration Number
- NL-OMON49977
- Lead Sponsor
- AB Science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 11
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
2.Patient with a familial or sporadic ALS
3.Patient aged between 18 and 75 years old inclusive at screening
4.Patient treated with a stable dose of Riluzole (100 mg/day) for at least 12
weeks prior to the baseline visit
5.Patient with an ALS disease duration from diagnosis no longer than 24 months
at screening
6. Patient with an ALSFRS-R total score progression between onset of the
disease and screening of
> 0.3 and <1.1 point/month
7.Patient with an ALSFRS-R total score decrease of * 1 point between screening
and baseline
8.Patient with an ALSFRS-R total score of at least 26 at screening following
rules below:
- at least 3 on item #3 and
- at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b,
#6, #7, #8, #9, #10, #11 and #12)
9.Patient with an ALSFRS-R total score of at least 25 at randomization
following rules below:
- at least 3 on item #3 and
- at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b,
#6, #7, #8, #9, #10, #11 and #12)
10. Contraception:
- Female patient of childbearing potential (entering the study 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 study and for 3 months and a half
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 study and for 3 months and a
half 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 study and for 3 months and a half after the last treatment
intake
Highly effective and effective methods of contraception are detailed in
appendix 15.1
11.Patient able to understand, and willing to sign, and date the written
informed consent form prior to any protocol-specific procedures. If verbal
consent is given, a Legal Representative of the patient must sign the informed
consent form
12.Patient able and willing to comply with study protocol and to come on-site
as per protocol visits schedule
13.Patient 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
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 hypersensitivity to masitinib excipients
3. Patient with an FVC < 60% predicted normal value for gender, height, and age
at screening
4. Patient with a weight < 41 kg and a BMI < 21 or > 30 kg/m² at screening and
at baseline
5. Pregnant, or nursing female patient
6. Patient with history (or family history) of severe skin toxicities or
reactions
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
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
- Anemia with Hgb < LLN and red blood cell count below the LLN
- Thrombocytopenia with platelets counts < 150 x 109/L
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 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
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)
- 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
11. Patient with active severe infection such as herpes, tuberculosis, viral
hepatitis, human immunodeficiency virus infection
12. Patient with autoimmune conditions such as systemic lupus erythematosus
13. Patient with a diagnosis of cancer or evidence of continued disease within
five years before screening
14. Patient with severe cardiac conditions:
- Patient with recent history of severe cardiovascular conditions including
acute myocardial infarction, unstable angina pectoris, coronary
revascularization procedure, congestive heart failure of NYHA Class III or IV,
stroke, including a transient ischemic attack
- Patient with cardiac conduction abnormalities at study entry including a QTc
Fredericia interval >450 milliseconds for males and >470 milliseconds for
females, a second- or third-degree atrioventricular block not successfully
treated with a pacemaker
- Patient presenting with edema of cardiac origin and left ventricular ejection
fraction * 50%
15. Patient with risk factors for sudden unexpected death of cardiovascular
origin
16. Patient who has been exposed to an investigational treatment within 3
months prior to screening
17. Patient who has been exposed to Edaravone within at least 30 days prior to
screening
18. Patient treated concomitantly with drugs known to interact with cytochrome
P450 (CYP450) isoenzymes (2C9, 2D6 and 3A4)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Absolute change from baseline of ALSFRS-R total score at week 48.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Progression free survival (PFS) defined as the time from randomization to<br /><br>progression (decline of more than 9 points in ALSFRS-R score from baseline) or<br /><br>death<br /><br>* Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSAQ-40) change<br /><br>* Forced Vital Capacity (FVC) change<br /><br>* Upper- and lower-limb muscle strength using hand-held dynamometry (HHD)<br /><br>* Clinician-rated Clinical Global Impression (CGI)<br /><br>* Combined Assessment of Function and Survival (CAFS)<br /><br>* Overall Survival (OS)<br /><br>* Event free survival (EFS) defined as the time from randomization to the first<br /><br>occurrence of either death or tracheostomy</p><br>