Evaluation of masitinib in Amyotrophic Lateral Sclerosis (ALS)

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2010-024423-24-GR
• Date of registration: 21/11/2013
• Prospective Registration: Yes
• Primary sponsor: ABScience
• Public title: Evaluation of masitinib in Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: A prospective, multicenter, randomized, double-blind, placebocontrolled, parallel groups, phase 2/3 study to compare the efficacy and safety of masitinib versus placebo in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS) - not applicable
• Date of first enrolment: 06/03/2015
• Target sample size: 381
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024423-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Czech Republic, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Portugal, Slovakia, Spain, United Kingdom, United States

Contacts

• Name: Alain Moussy
• Affiliation: ABScience

• Name: Alain Moussy
• Affiliation: ABScience

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female or male patient aged between 18 and 75 years of age, with a weight > 50 kg and BMI between 18 and 35 kg/m².
2. Familial or sporadic ALS
3. Patient diagnosed with laboratory supported, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (Brooks, 1994)
4. Disease duration from symptoms onset no longer than 36 months at the screening visit
5. Patient treated with a stable dose of riluzole (100 mg/day) for at least 30 days prior to screening
6. Patient with a FVC (Forced Vital Capacity) equal to or more than 60% predicted normal value for gender, height, and age at the screening visit
7. Patient with life expectancy = 6 months
8. Patient with adequate organ function at screening and baseline:
• Absolute Neutrophils Count (ANC) = 2 x 109/L
• Hemoglobin = 10 g/dL
• Platelets (PTL) = 100 x 109/L
• AST/ALT = 3 ULN
• Bilirubin = 1.5 ULN
• Albuminemia > 1 x LLN
• 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
9. Male patient or female Female patient of child bearing potential, (entering the study after a menstrual period and who have a negative pregnancy test)), who must agreeagrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.
10. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. Male patients must use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception (with failure rate < 1%) during the study and for three3 months after the last treatment intake.
11. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
12. Patient able and willing to comply with study procedures as per p?otocol
13. Patient able to understand, and willing to sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
14. 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, during the first two months of treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 227
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 154

Exclusion criteria:
1. Patient with history of cardiac, hematologic, hepatic, respiratory disorder that is clinically significant for his/her participation in the study
2. Patient who underwent tracheotomy and /or gastrostomy
3. Patient with a diagnosis of cancer or evidence of continued disease within five years before starting study treatment
4. Patient with significant sensory abnormalities, dementia, other neurologic diseases, uncompensated medical illness, substance abuse and psychiatric illness
5. Patient who have participated in a clinical trial within 3 months prior to screening
6. Pregnant, or nursing female patient
7. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection
8. Patient with known active hepatitis B, hepatitis C or tuberculosis
9. Patient with any severe and/or uncontrolled medical condition
10. Patient having cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
11. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
PREVIOUS TREATMENTS WASH OUT
12. Patient treated with any investigational agent within 3 months prior to screening



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Patients suffering from Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 17.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: na
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: na
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 48

Main Objective: The objective is to compare the efficacy and safety of masitinib versus placebo in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS).

Secondary Objective: • CAFS
• Survival (time from randomisation to the date of death or first tracheotomy)
• Time to first tracheotomy (time from randomisation to the time of the first tracheotomy)
•Change of FVC from baseline to each time point (W4, 8, 12, 24, 36, 48)
•Number of failure (a 9-point drop in ALSFRS-R) from baseline or death
• Change from baseline to each time point (W4, 8, 12, 24 and 36) in ALSFRS-R at W4, 8, 12, 24 & 36
• Number of failure ( a 6-point drop in ALSFRS-R or death) from baseline
• Overall survival from randomization to date of death
• Survival rate (rate of patients alive without tracheotomy at each time point (W12, 24, 36 & 48))
• Change in cystatin C level from baseline to each time point
• FVC score at W4, 8, 12, 24, 36
• Time to first gastrectomy (the time from randomisation to the time of the first gastrectomy)
• Absolute & relative change from baseline in ALSAQ- 40 at each time point
• Safety: occurrence of AE, changes on clinical examination

Primary end point(s): Absolute change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised

Secondary Outcome(s)

Secondary end point(s): • Combined Assessment of Function and Survival (CAFS)
• Survival (time from randomisation to the date of death or first tracheotomy)
• Time to first tracheotomy (time from randomisation to the time of the first tracheotomy)
•Change of FVC from baseline to each time point (W4, 8, 12, 24, 36, 48)
•Number of failure (a 9-point drop in ALSFRS-R) from baseline or death
• Change from baseline to each time point (W4, 8, 12, 24 and 36) in ALSFRS-R at W4, 8, 12, 24 & 36
• Number of failure ( a 6-point drop in ALSFRS-R or death) from baseline
• Overall survival from randomization to date of death
• Survival rate (rate of patients alive without tracheotomy at each time point (W12, 24, 36 & 48))
• Change in cystatin C level from baseline to each time point
• FVC score at W4, 8, 12, 24, 36
• Time to first gastrectomy (the time from randomisation to the time of the first gastrectomy)
• Absolute & relative change from baseline in ALSAQ- 40 at each time point
• Safety: occurrence of AE, changes on clinical examination n including vital signs (blood pressure, pulse rate) and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis)

Timepoint(s) of evaluation of this end point: Week 4, 8, 12, 24, 36

Secondary ID(s)

2010-024423-24-ES

AB10015

Source(s) of Monetary Support

ABScience