A prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare the efficacy and the safety of masitinib at 6 mg/kg/day versus placebo in the treatment of patients with Severe Persistent Asthma treated with oral corticosteroids

• Register: EUCTR
• Last refreshed on: 5 June 2017
• Main ID: EUCTR2010-020803-63-SK
• Date of registration: 04/04/2013
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare the efficacy and the safety of masitinib at 6 mg/kg/day versus placebo in the treatment of patients with Severe Persistent Asthma treated with oral corticosteroids
• Scientific title: A prospective, multicenter, randomised, double-blind, placebo-controlled, 2-parallel groups, Phase 3 study to compare the efficacy and the safety of masitinib at 6 mg/kg/day versus placebo in the treatment of patients with Severe Persistent Asthma treated with oral corticosteroids
• Date of first enrolment: 22/10/2013
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020803-63
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, France, Germany, Greece, Hungary, Slovakia, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with Severe Persistent Asthma and already treated with oral corticosteroids at a minimal daily dose of 5 mg prednisone or equivalent for at least 3 months prior to screening visit
2. Patient with history of asthma = 1 year prior to screening visit who also meet the following criteria:
o baseline FEV1 = 35 to = 80% of the predicted normal value, demonstrated at least 6 hours after short-acting beta-2-agonist or 12 hours after long-acting beta-2-agonist
o at least 2 asthma exacerbations within one year prior to screening visit including one severe asthma exacerbation as per protocol definition
o uncontrolled asthma
3. Patient with no significant change in the regular asthma medication, no severe asthma exacerbation for at least 4 weeks prior to screening visit
4. Non-smoker patient for at least one year and with a prior tobacco consumption < 10 packs/year
5. Patient with normal organ function defined as:
o Absolute neutrophil count (ANC) = 2.0 x 109/L
o Haemoglobin = 10 g/dL
o Platelets (PTL) = 100 x 109/L
o AST/ALT = 2.5x ULN
o Bilirubin = 1.5x ULN
o Creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
o Albumin > 1 LLN
o Urea = 1.5 x ULN
o Proteinuria < 30 mg/dL on the dipstick; in case of proteinuria = 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
6. Male or female patient older than 18 years
7. Patient weight > 45 kg and BMI > 18 kg/m²
8. Male or female patient of child bearing potential (entering the study after a menstrual period and who have a negative pregnancy test) must agree to use two 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
9. Patient able and willing to comply with study procedures as per protocol;
10. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
11. Patient affiliated to a social security regimen
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Female patient who is pregnant or lactating
2. Asthmatic patient still exposed to allergens or to triggering factors influencing asthma control
3. Patient with history of acute infectious sinusitis or respiratory tract infection within 4 weeks prior to screening visit
4. Patient presenting with cardiac disorders defined by at least one of the following conditions will be excluded:
a. Ischemic heart disease, defined by at least one of the following conditions:
i. Medical history of ischemic heart disease
ii. Clinical symptoms of ischemic heart disease
iii. Q wave > 3 mm on the electrocardiogram
iv. ST elevation or depression > 2 mm on the electrocardiogram
v. Negative T wave in at least 2 leads of the electrocardiogram
b. Cardiac failure, defined by at least one of the following conditions:
i. Medical history of cardiac failure defined by a previous left ventricular ejection fraction = 50%
ii. Clinical symptoms of cardiac failure
iii. Current treatment for cardiac failure
iv. NT Pro-BNP = 300 pg/mL or BNP = 75 pg/mL and/or troponin T > 0.1 ng/mL or troponin I > 0.35 ng/mL
c. Conduction disorders or arrhythmia, defined by at least one of the following and confirmed by electrocardiogram:
i. Severe ventricular arrhythmia (frequent premature ventricular beats)
ii. Atrioventricular block at second or third level
iii. Left bundle branch block
5. Patient with active lung disease other than asthma (e.g. chronic bronchitis)
6. Patient who had a major surgery within 2 weeks prior to screening visit
7. Patient with life expectancy < 6 months
8. Patient with history of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ
9. Patient with any severe and/or uncontrolled medical condition
10. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection
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
12. Patient with inadequate wash-out time at the screening visit:
Wash-out time for prohibited concomitant asthma medications:
Treatment with the following non-steroidal controllers has to be stopped about 24 h prior to screening visit: sustained-release theophylline, leukotriene antagonists, lipoxygenase inhibitors, inhaled anticholinergics, oral beta2-agonists, inhaled disodium cromoglycate, inhaled nedocromil.
Wash-out time for allowed concomitant asthma medications
• Long acting Beta agonists (12h prior to screening visit)
• Short acting agonists (6h prior to screening visit)
13. Patient treated with prohibited medications

RANDOMISATION CRITERIA (to be checked at W0):
1. Good study treatment (i.e. placebo) compliance (=80%) during the 2-week run-in period
2. Daily mean symptom score = 2 during the 2-week run in period
3. No asthma exacerbation (moderate or severe) during the 2-week run in period



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

Health Condition(s) or Problem(s) studied

Severe Persistent Asthma
MedDRA version: 14.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
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)

Main Objective: The objective is to compare the efficacy and the safety of masitinib at 6 mg/kg/day versus placebo in the treatment of patients with Severe Persistent Asthma treated with oral corticosteroids.
Primary endpoint: Asthma exacerbation rate (severe and moderate exacerbations) at 36 weeks adjusted on the available person-time (time to end of treatment)

Primary end point(s): Asthma exacerbation rate (severe and moderate exacerbations) at 36 weeks adjusted on the available person-time (time to end of treatment)

Timepoint(s) of evaluation of this end point: Asthma exacerbation rate (severe and moderate exacerbations) at 36 weeks adjusted on the available person-time (time to end of treatment)

Secondary Objective: • Asthma Control Questionnaire (ACQ) Score at 12, 20, 28 and 36 weeks
• Moderate and severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Time to first asthma exacerbation (severe or moderate)
• Percentage of patient experiencing at least one exacerbation at 12, 20, 28 and 36 weeks
• Asthma symptom score at all time points
• Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), Forced Expiratory Flow between 25-75% of FVC (FEF25-75) at 12, 20, 28 and 36 weeks
• Morning and evening Peak Expiratory Flow Rate (PEFR) at 12, 20, 28 and 36 weeks
• Use of rescue medication for asthma at 12, 20, 28 and 36 weeks
• Quality of Life assessment: AQLQ score at each visit at 12, 20, 28 and 36 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Asthma Control Questionnaire (ACQ) Score at 12, 20, 28 and 36 weeks
• Moderate and severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Percentage of patient experiencing at least one exacerbation at 12, 20, 28 and 36 weeks
• Asthma symptom score at all time points
• Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), Forced Expiratory Flow between 25-75% of FVC (FEF25-75) at 12, 20, 28 and 36 weeks
• Morning and evening Peak Expiratory Flow Rate (PEFR) at 12, 20, 28 and 36 weeks
• Use of rescue medication for asthma at 12, 20, 28 and 36 weeks
• Quality of Life assessment: AQLQ score at each visit at 12, 20, 28 and 36 weeks

Secondary end point(s): • Asthma Control Questionnaire (ACQ) Score at 12, 20, 28 and 36 weeks
• Moderate and severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Severe asthma exacerbation rate at 12, 20, 28 and 36 weeks
• Time to first asthma exacerbation (severe or moderate)
• Percentage of patient experiencing at least one exacerbation at 12, 20, 28 and 36 weeks
• Asthma symptom score at all time points
• Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), Forced Expiratory Flow between 25-75% of FVC (FEF25-75) at 12, 20, 28 and 36 weeks
• Morning and evening Peak Expiratory Flow Rate (PEFR) at 12, 20, 28 and 36 weeks
• Use of rescue medication for asthma at 12, 20, 28 and 36 weeks
• Quality of Life assessment: AQLQ score at each visit at 12, 20, 28 and 36 weeks

Secondary ID(s)

AB07015

2010-020803-63-FR