Clinical study for the assessment of the efficacy and the safety of masitinib versus placebo in the treatment of patients with severe COPD with elevated eosinophils level.

• Register: EUCTR
• Last refreshed on: 4 January 2016
• Main ID: EUCTR2012-005586-13-GR
• Date of registration: 14/12/2015
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Clinical study for the assessment of the efficacy and the safety of masitinib versus placebo in the treatment of patients with severe COPD with elevated eosinophils level.
• 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)
• Date of first enrolment: 21/12/2015
• Target sample size: 45
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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: 2

Countries of recruitment

Greece, Spain, Ukraine, United Kingdom

Contacts

• Name: Volodymyr ZASTAVNYI
• Affiliation: AB Science

• Name: Volodymyr ZASTAVNYI
• 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 elevated eosinophils levels : >= 150/?L
3. Patient with at least one exacerbation during the preceding year.
4. Patient with FEV1/FVC ratio (post-bronchodilator) ? 70%.
5. Patient with FEV1 (post-bronchodilator) between = 30 % and ? 50 % of predicted value
6. Patient pre-treated with adequate and stable symptomatic treatment for at least 3 months prior to screening visit.
7. 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
8. 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
• ßilirubin = 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.
9. Male or female patient, aged 40 to 75 years inclusive, weight > 50 kg and BMI between 18 and 35 kg/m²
10. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective 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. ?hese include:
• A documented placement of an intrauterine device (IUD) or system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
• Documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used
• Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
• Any other contraceptive method with a documented failure rate of <1% per year
• Abstinence
11. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. These include:
• Condom;
• If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must use two highly effective 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. These are:
• Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
• Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);
• Your female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method
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

Severe Chronic Obstructive Pulmonary Disease (COPD) with elevated eosinophil
MedDRA version: 18.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease 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-
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: 790-299-79-5
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)

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

Main Objective: The objective is to compare the efficacy and the safety of masitinib versus placebo in the treatment of patients with severe COPD with elevated eosinophils level.

Primary endpoint:
• Absolute change from baseline in the 6-minutes walking distance test at Week 24

Secondary Objective: • Absolute change from baseline (W0) in the 6-minutes walking distance test at Week 4, 8, 12, 16 and 20
• Absolute change from baseline (W0) in the post-bronchodilator FEV1 at Week 4, 8, 12, 16, 20 and 24
• Absolute change from baseline (W0) over 24 weeks in the weekly dose of rescue medication (salbutamol)
• Absolute change from baseline (W0) in the TDI Focal Score (i.e. change from BDI or Baseline Dyspnoea Index at baseline (W0) over 24 weeks of treatment
• Absolute change from baseline (W0) in the SGRQ at Week 4, 8, 12, 16, 20 and 24
• Absolute change from baseline (W0) until Week 4, 8, 12, 16, 20 and 24 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

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

Secondary Outcome(s)

Secondary end point(s): • Absolute change from baseline (W0) in the 6-minutes walking distance test at Week 4, 8, 12, 16 and 20
• Absolute change from baseline (W0) in the post-bronchodilator FEV1 (Forced Expiratory Volume in one second) at Week 4, 8, 12, 16, 20 and 24
• Absolute change from baseline (W0) over 24 weeks in the weekly dose of rescue medication (salbutamol)
• Absolute change from baseline (W0) in the TDI (Transitional Dyspnoea Index) Focal Score (i.e. change from BDI or Baseline Dyspnoea Index at baseline (W0)) over 24 weeks of treatment
• Absolute change from baseline (W0) in the SGRQ (Saint George Respiratory Questionnaire) at Week 4, 8, 12, 16, 20 and 24
• Absolute change from baseline (W0) until Week 4, 8, 12, 16, 20 and 24 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
• Absolute change from baseline (W0) in anti-inflammatory laboratory parameter C-reactive protein (CRP) at Week 24
• Absolute change from baseline (W0) in further spirometry parameters (IC, FVC) at Week 4, 8, 12, 16, 20 and 24
• Absolute change from baseline (W0) in plethysmography parameters (IC or Inspiratory Capacity, FRC or Functional Residual Capacity, RV or Residual Volume) at Week 4, 8, 12, 16, 20 and 24.

Timepoint(s) of evaluation of this end point: Week 4, 8, 12, 16, 20 and 24

Secondary ID(s)

2012-005586-13-ES

AB12009

Source(s) of Monetary Support

AB Science