A prospective, multicentre, randomised, double-blind, placebo-controlled, phase 2a study to compare the efficacy and the safety of 24-week treatment with masitinib versus placebo in patients with severe Chronic Obstructive Pulmonary Disease (COPD)

• Register: EUCTR
• Last refreshed on: 28 May 2018
• Main ID: EUCTR2012-005586-13-ES
• Date of registration: 24/06/2013
• Prospective Registration: Yes
• Primary sponsor: AB SCIENCE
• Public title: A prospective, multicentre, randomised, double-blind, placebo-controlled, phase 2a study to compare the efficacy and the safety of 24-week treatment with masitinib versus placebo in patients with severe Chronic Obstructive Pulmonary Disease (COPD)
• Scientific title: A prospective, multicentre, randomised, double-blind, placebo-controlled, phase 2a study to compare the efficacy and the safety of 24-week treatment with masitinib versus placebo in patients with severe Chronic Obstructive Pulmonary Disease (COPD) - COPD
• Date of first enrolment: 19/08/2013
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005586-13
• 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): no Therapeutic use (Phase IV): no

Countries of recruitment

Greece, Slovakia, Spain

Contacts

• Name: Frédérique GRAPIN
• Affiliation: AB SCIENCE

• Name: Frédérique GRAPIN
• Affiliation: AB SCIENCE

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with history of chronic obstructive pulmonary disease for at least 12 months prior to screening visit (ATS/ERS 2005) and chronic productive cough for 3 months in each of the 2 years prior to screening visit (if other causes of productive cough have been excluded), and present during the 4 weeks preceding screening.
2. Patient with at least one exacerbation during the preceding year.
3. Patient with FEV1/FVC ratio (post-bronchodilator) ? 70%.
4. Patient with FEV1 (post-bronchodilator) between ? 30 % and ? 50 % of predicted value
5. Patient pre-treated with adequate and stable symptomatic treatment for at least 3 months prior to screening visit.
6. Former smoker (defined as: smoking cessation at least one year ago) or current smoker both with a smoking history of at least 10 pack years
7. Patient with normal organ function defined as:
? absolute neutrophils count (ANC) ? 2.0 x 109/L,
? haemoglobin ? 10 g/dL
? platelets (PTL) ? 100 x 109/L
? AST/ALT ? 3x ULN
? bilirubin ? 1.5x ULN
? creatinin clearance ? 60 mL/min
? albumin > 1 x LLN
? Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ? 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours.
8. Male or female patient, aged 40 to 75 years inclusive, weight > 50 kg and BMI between 18 and 35 kg/m²
9. Man and woman of child bearing potential, 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.
10. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
11. Patient able and willing to comply with study procedures as per protocol.
12. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months.
13. Patient able to understand, sign, and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures.
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Pregnant, or nursing female patient
2. Patient experiencing COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to the screening visit.
3. Patient with lower respiratory tract infection not resolved 4 weeks prior to the screening visit.
4. Patient with asthma and/or other relevant lung disease (e.g. history of bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], and active tuberculosis).
5. Patient currently participating in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the screening visit.
6. Patients with known alpha-1-antitrypsin deficiency.
7. Patient with clinically significant cardiopulmonary abnormalities (diagnosed clinically or by X-ray / CT-scan / ECG) that are not related to COPD and that require further evaluation.
8. Patient who had major surgery within 2 weeks prior to screening visit
9. Patient presenting with 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
10. Patient with:
? Life expectancy < 6 months
? < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ
? Any severe and/or uncontrolled medical condition
? Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection, tuberculosis...)
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. Treatment with any investigational agent within 4 weeks prior baseline


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

Health Condition(s) or Problem(s) studied

Patients with severe COPD

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: 790-299-29-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB
Concentration unit: mg/kg milligram(s)/kilogram
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: 790-299-29-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB
Concentration unit: mg/kg milligram(s)/kilogram
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)

Secondary Objective: ? Absolute change from randomisation in the 6-minutes walking distance test at Week 4, 8 , 12, 18 and 24.
? Absolute change from randomisation in the post-bronchodilator FEV1 (Forced Expiratory Volume in one second) at Week 4, 8, 12, 18 and 24.
? Absolute change from randomisation over 24 weeks in the weekly dose of rescue medication (salbutamol)
? Absolute change from randomisation in the TDI (Transitional Dyspnoea Index) Focal Score (i.e. change from BDI or Baseline Dyspnoea Index at randomisation [W0]) over 24 weeks of treatment
? Absolute change from randomisation in the SGRQ (Saint George Respiratory Questionnaire) at Week 4, 8, 12, 18 and 24
? Absolute change from randomisation in symptoms of cough and sputum
? Exacerbation rate (number of COPD exacerbation per patient per year) during the W0 W24 period
? Rate of Severe exacerbations defined as a need for hospitalization or emergency department visit during the W0 W24 period
(etc...)

Main Objective: The objective is to compare the efficacy and the safety of masitinib at 3 mg/kg/day or 4.5 mg/kg/day versus placebo in the treatment of patients with severe COPD.
Primary endpoint:
? Absolute change from randomisation in the 6-minutes walking distance test at Week 24

Primary end point(s): Absolute change from randomisation in the 6-minutes walking distance test at Week 24

Timepoint(s) of evaluation of this end point: 24 WEEKS

Secondary Outcome(s)

Secondary end point(s): ? Absolute change from randomisation in the 6-minutes walking distance test at Week 4, 8 , 12, 18 and 24.
? Absolute change from randomisation in the post-bronchodilator FEV1 (Forced Expiratory Volume in one second) at Week 4, 8, 12, 18 and 24.
? Absolute change from randomisation over 24 weeks in the weekly dose of rescue medication (salbutamol)
? Absolute change from randomisation in the TDI (Transitional Dyspnoea Index) Focal Score (i.e. change from BDI or Baseline Dyspnoea Index at randomisation [W0]) over 24 weeks of treatment
? Absolute change from randomisation in the SGRQ (Saint George Respiratory Questionnaire) at Week 4, 8, 12, 18 and 24
? Absolute change from randomisation in symptoms of cough and sputum
? Exacerbation rate (number of COPD exacerbation per patient per year) during the W0 W24 period
? Rate of Severe exacerbations defined as a need for hospitalization or emergency department visit during the W0 W24 period
(etc...)

Timepoint(s) of evaluation of this end point: the same duration of the study

Secondary ID(s)

AB12009

Source(s) of Monetary Support

AB SCIENCE