Masitinib in the Treatment of Patients With Severe Uncontrolled Asthma and Elevated Eosinophil Levels

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

The purpose of this study is to assess the safety and efficacy of masitinib (6 mg/kg/day) in severe persistent asthma, uncontrolled with high dose of inhaled corticosteroid and with elevated eosinophil levels.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Masitinib

Detailed Description

Masitinib is a selective tyrosine kinase inhibitor. It is known that activation of inflammatory cells, such as mast cells, and fibrous tissue remodeling are associated with c-Kit, Lyn and PDGFR kinase signaling pathways; all key targets of masitinib. This is a multicenter, double-blind, randomized, parallel-group (ascending dose titration of masitinib to 6.0 mg/kg/day and matching placebo), comparative study of oral masitinib in the treatment of patients with severe asthma, uncontrolled with high dose of inhaled corticosteroid and with elevated eosinophil levels. Eligible patients will be treated during at least 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Centro Respiratorio Quilmes
• Malaysia
  • Kuching, Malaysia, 93586
    • Sarawak General Hospital
• Peru
  • Miraflores, Peru
    • Clinica Universidad de Los Andes
• Philippines
  • Quezon City, Philippines
    • The Philippine Heart Center
• Ukraine
  • Kiev, Ukraine, 03680
    • National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main inclusion criteria include:

• 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 inhaled corticosteroids (ICS) / long-acting beta2-agonists (LABA) combination therapy.
• Patient with elevated eosinophil level related to asthma at baseline: ≥0.15 K/uL or patient with eosinophil level ≥0.15 K/uL related to asthma demonstrated in the year prior to screening
• Non-smoker patient for at least one year and with a prior tobacco consumption <10 packs/year

Main exclusion criteria include:

• Female patient who is pregnant or lactating
• Asthmatic patient still exposed to allergens or to triggering factors influencing asthma control
• Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary Function Tests
• 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)
• Patient with history of acute infectious sinusitis or respiratory tract infection within 4 weeks prior to screening visit
• Patient with active lung disease other than asthma (e.g. chronic bronchitis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants receive matched placebo	Drug: Placebo; Other Names: Placebo Oral Tablet
Experimental: Masitinib (titration to 6.0 mg/kg/day); Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.	Drug: Masitinib; Other Names: AB1010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe asthma exacerbation rate	The number of severe asthma exacerbations over time frame of outcome measure	Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma exacerbation rate	The number of asthma exacerbations over time frame of outcome measure	Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months
Asthma Control Questionnaire (ACQ)	Asthma Control Questionnaire (ACQ); Type of questionnaire-description: A simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment.; Number of items: 7 items; 1 week recall (for items on symptoms and rescue inhaler use); Number of domains & categories: ACQ has a multidimensional construct assessing symptoms (5 items--self-administred) and rescue inbronchodilator use (1 item-self-administered), and FEV1% (1 item) completed by clinic staff; Scaling of items: 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 categories for FEV1%). Scores range between 0 (totally controlled) and 6 (severely uncontrolled).	48 weeks

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Lavinia Davidescu, MD, PhD, University of Medicine and Pharmacy Oradea, Oradea, Romania.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Eosinophil; Tyrosine kinase inhibitor; Severe persistent asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: AB14001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No