severe Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 12.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease
Conditions
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion 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 = 2.5x ULN • bilirubin = 1.5x ULN • creatinin = 1.5 x ULN • albumin > 1 x LLN • urea = 1.5 x ULN • dipstick proteinuria 45 kg and with BMI > 18kg/m² at screening 9. Man and woman of child bearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) 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. Patient able and willing to comply with study procedures as per protocol. 11. Patient able to understand, sign, and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures. 12. Patient affiliated to a social security system. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 having cardiac disorders defined by at least one of the following conditions: a. Ischemic heart disease, defined by at least one of the following condition: i. Medical history of ischemic heart disease ii. Clinical symptoms of ischemic heart disease iii. Q wave > 3 mm on the electrocardiogram iv. ST elevation or depression > 2 mm on the electrocardiogram v. Negative T wave in at least 2 leads of the electrocardiogram b. Cardiac failure, defined by at least one of the following condition: i. Medical history of cardiac failure defined by a previous left ventricular ejection fraction = 50% or a current treatment for cardiac failure ii. Clinical symptoms of cardiac failure iii. NT proBNP = 300 pg/mL or BNP = 75 pg/mL or troponin T > 0.1 ng/mL or troponin I > 0.35 ng/mL c. Conduction disorders or arrhythmia, defined by at least one of the following and confirmed by electrocardiogram : i. Severe ventricular arrhythmia (frequent premature ventricular beats) ii. Atrioventricular block at second or third level iii. Left bundle branch block 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 Known diagnosis of human immunodeficiency virus (HIV) infection 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 RANDOMISATION: To be randomised into the double-blind treatment period the following criteria must be fulfilled at baseline [W0]: 1. No moderate or severe COPD exacerbations between screening visit and baseline or W0 visit 2. Tablet compliance = 80%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to compare the efficacy and the safety of masitinib at 6 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): -minutes walking distance. The test is performed on subjects free of diseases, which could interfere with performance in a walking test. Tests must be performed in a quiet 50-m long hospital corridor. Patients must be encouraged every 30 s to continue walking as quickly as possible.;Secondary Objective: Absolute change from randomisation in the 6-minutes walking distance test at each time point. 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 | — |
Countries
France
Outcome results
None listed