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

• ClinicalTrials.gov Identifier: NCT03771040
• Recruitment Status: Completed
• First Posted: December 10, 2018
• Last Update Posted: December 8, 2020
• Sponsor: AB Science
• Information provided by (Responsible Party): AB Science

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Masitinib; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 347 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: September 2020
• Actual Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
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 Name: AB1010
Placebo Comparator: Placebo; Participants receive matched placebo	Drug: Placebo; Other Name: Placebo Oral Tablet

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Asthma exacerbation rate [ Time Frame: Duration of patient treatment exposure, assessed until withdrawal from study, study completion date, or for a maximum of 60 months ]
   The number of asthma exacerbations over time frame of outcome measure
2. Asthma Control Questionnaire (ACQ) [ Time Frame: 48 weeks ]

   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

Argentina

Centro Respiratorio Quilmes

Buenos Aires, Argentina

Malaysia

Sarawak General Hospital

Kuching, Malaysia, 93586

Peru

Clínica Universidad de los Andes

Miraflores, Peru

Philippines

The Philippine Heart Center

Quezon City, Philippines

Ukraine

National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine

Kiev, Ukraine, 03680

Sponsors and Collaborators

AB Science

Investigators

• Principal Investigator: Lavinia Davidescu, MD, PhD; University of Medicine and Pharmacy Oradea, Oradea, Romania.

More Information

• Responsible Party: AB Science
• ClinicalTrials.gov Identifier: NCT03771040
• Other Study ID Numbers: AB14001
• First Posted: December 10, 2018
• Last Update Posted: December 8, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by AB Science:

Severe persistent asthma; Eosinophil; Tyrosine kinase inhibitor

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases