To compare the efficacy and the safety of Masitinib versus placebo in the treatment of patients with severe Asthma

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/11/010315
• Date of registration: 01-11-2017
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: To compare the efficacy and the safety of Masitinib versus placebo in the treatment of patients with severe Asthma
• Scientific title: A prospective, multicenter, randomised, double-blind, placebo-controlled, phase 3 study to compare the efficacy and the safety of masitinib versus placebo in the treatment of patients with severe uncontrolled asthma and elevated eosinophil levels
• Date of first enrolment: 01-12-2017
• Target sample size: 345
• Recruitment status: Suspended
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=17135
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Other Method of allocation concealment:Other Blinding and masking:Double Blind Double Dummy
• Phase: Phase 3

Countries of recruitment

Algeria, Argentina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Egypt, Greece, India, Israel, Italy, Lebanon, Malaysia, Mexico, Morocco, Peru, Philippines, Poland, Romania, Slovakia, Spain, Taiwan, Thailand, Tunisia, Ukraine

Contacts

• Name: Dr Aashima Punyani
• Affiliation: Apothecaries Clinical Research LLP

• Name: Dr Aashima Punyani
• Affiliation: Apothecaries Clinical Research LLP

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients with a physician diagnosis of persistent asthma for at least 12 months based on Global Initiative for Asthma (GINA) 2009 Guidelines whose asthma is partially controlled or uncontrolled on ICS/LABA combination therapy based on the following criteria.



a) A well-documented requirement for regular treatment with a minimum dose of either fluticasone/salmeterol combination therapy (DPI formulation: 500/50 μg BID or MDI formulation: 460/42 μg BID), or budesonide/formoterol combination therapy (320/9 μg BID), or mometasone/formoterol combination therapy (400/10 μg BID) in the 12 months prior to screening with or without maintenance oral corticosteroids (OCS)



b) Forced expiratory volume (FEV1) ï?³ 35 to < 80% predicted normal during the screening phase (3 attempts maximum) and on the randomization day prior to the first dose of IMP (3 attempts maximum).



c)Reversibility of at least 12% and 200 ml in FEV1 after 200 μg to 400 μg (2 to 4 inhalations) of albuterol during the screening phase (3 attempts maximum), or documented history of a reversibility test that met this criteria within 12 months prior to screening, or documented history of bronchial hyperreactivity from a positive methacholine challenge (PD20 methacholine <= 8 mg) within 12 months prior to screening



d) Within the 12 months prior to screening at least 2 severe asthma exacerbations while treated with stable dose for at least 2 weeks of either fluticasone/salmeterol combination therapy (DPI formulation: 500/50 μg BID or MDI formulation: 460/42 μg BID), or budesonide/formoterol combination therapy (320/9 μg BID), or mometasone/formoterol combination therapy (400/10 μg BID).

Severe asthma exacerbation is defined by any of the following events:

-Treatment with 1 or more systemic (oral and/or parenteral) steroid bursts for worsening asthma

-In-patient hospitalization or an emergency care visit for worsening asthma


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. Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary Function Tests

4. Within 12 weeks prior to screening, patient who received oral corticosteroids for any other reason than to treat severe asthma exacerbation (patients needing long term corticosteroids intake to control basal asthma condition)

5. Patient with history of acute infectious sinusitis or respiratory tract infection within 4 weeks prior to screening visit

6. Patient presenting with cardiac disorders defined by at least one of the following conditions will be excluded:

a. Patient with recent cardiac history (within 6 months) of:

i. Acute coronary syndrome

ii. Acute heart failure (class III or IV of the NYHA classification)

iii. Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)

b. Patient with cardiac failure class III or IV of the NYHA classification

c. Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)

d. Syncope without known aetiology within 3 months

e. Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension

7. Patient with active lung disease other than asthma (e.g. chronic bronchitis)

8. Patient who had a major surgery within 2 weeks prior to screening visit

9. Patient with life expectancy < 6 months

10. Patient with history of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ

11. Patient with any severe and/or uncontrolled medical condition

12. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection

13. 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

14. Patient treated with prohibited medication or inadequate wash-out time at the screening visit:









Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: J984- Other disorders of lung Health Condition 2: null- Severe uncontrolled Asthma and elevated eosinophils level

Intervention(s)

Intervention1: Masitinib mesylate

Chemical name: 4-[(4-methyl-piperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-
yl)-1,3-thiazol-2-yl]amino}-phenyl) benzamide, methane sulphonic acid salt.

CAS number: masitinib: 790 299-79-5: Masitinib Dose: 6mg/kg/day
and standard treatment (fluticasone and salmeterol)

Frequency: 2 times a day
ROA: Oral
Total duration of Therapy: 48 weeks

Control Intervention1: Placebo and standard treatment: Placebo along with standard treatment (fluticasone/salmeterol)


Frequency: 2 times a day
ROA: Oral
Total duration of Therapy: 48 weeks

Primary Outcome(s)

Primary endpoint:

Severe Asthma exacerbation rate adjusted on the available person-time (time to end of treatment)









Timepoint: 48 weeks

Secondary Outcome(s)

Secondary endpoints:

1. Absolute change from baseline to week 48 in Asthma Control Questionnaire (ACQ)

2. Absolute change from baseline to each time point (week 12, 24 and 36) in Asthma Control Questionnaire (ACQ)

3. Absolute change from baseline to week 48 in Forced Expiratory Volume in one second(FEV1)

4. Absolute change from baseline to each time point (week 4, 8, 12, 24 and 36) in Forced Expiratory Volume in one second(FEV1)







Timepoint: 1. Absolute change from baseline to each time point (week 4, 8, 12, 24, 36) in Forced Vital Capacity (FVC)

Secondary ID(s)

AB 14001, Version. 3.0 dated 31-Oct-16

Source(s) of Monetary Support

AB Science, 3 avenue George V, 75008 Paris, France

Secondary Sponsor(s)

Apothecaries Clinical Research LLP

Ethics review

Status: Approved
Approval date: 01/12/2017
Contact:

SCCMH Institutional Ethics Committee Dr Chetan Kumar NG

Status: Approved
Approval date: 01/12/2017
Contact:

SCCMH Institutional Ethics Committee Dr K S Satish

Status: Not Approved
Approval date:
Contact:

Dr BR Ambedkar Medical College Banglore KK Shyamala

Status: Not Approved
Approval date:
Contact:

NG Hospital Institutional Ethics Committee Jayamohan Unninathan

Status: Not Approved
Approval date:
Contact:

NG Hospital Institutional Ethics Committee k Arul