Asthma Respiratory Asthma uncontrolled on medium doses of inhaled corticosteroids in combination with long-acting ß2- agonists
Conditions
Interventions
It is expected that approx. 1,400 participants will be included in the study in about 200 sites in approx. 16 countries. It will last 30 weeks with 7 visits in total.
At the first vis
Sponsors
Chiesi Farmaceutici S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: Subject’s written informed consent obtained prior to any study related procedures; 2. Gender and age: Male or female subjects aged =18 and =75 years; 3. Diagnosis of asthma: A documented diagnosis of permanent asthma for at least 1 year according to GINA recommendations (Box 1-2, GINA report 2021), and with diagnosis before the subject’s age of 40 years; 4. Stable asthma therapy: a stable treatment with medium dose of Inhaled corticosteroids (ICS) (extrafine BDP daily dose >200 and =400 µg or estimated clinically comparable dose) plus a long-acting ß2-agonist (LABA) (formoterol 24 µg or salmeterol 100 µg or vilanterol 25 µg or other approved dose of LABA as clinically comparable to the others) for at least 4 weeks prior to screening; 5. Lung function: A pre bronchodilator FEV1 12% and >200 mL over baseline within 30 minutes after inhaling 400 µg of salbutamol pMDI (based on ATS/ERS guidelines); 7. A Post-bronchodilator FEV1/FVC ratio =0.5 within 30 minutes after inhaling 400 µg of salbutamol pMDI at screening (based on ATS/ERS guidelines); 8. Poor Asthma control: Evidence of poorly controlled or uncontrolled asthma as based on an Asthma Control Questionnaire© (ACQ-7) score =1.5 at screening and at randomisation; 9. History of exacerbations: A documented history of one or more asthma exacerbations requiring treatment with systemic corticosteroids or emergency department visit or inpatient hospitalisation in the last 3 years prior to screening; 10. A cooperative attitude and ability: 10.1 to correctly use the pMDI inhalers; 10.2 to perform all trial related procedures including technically acceptable pulmonary function tests; 10.3 to correctly use the e-Diary/e-Peak flow meter and home-spirometry device. 11. Female subjects: 11.1. Woman of Childbearing Potential (WOCBP) fulfilling one of the following criteria: 11.1.1. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up call or 11.1.2. WOCBP with non-fertile male partners (contraception is not required in this case). 11.2. Female patient of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator’s request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges).
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating woman where pregnancy is defined as the state of a female after conception and until termination of the gestation, confirmed by a positive pregnancy test (serum pregnancy test to be performed at screening visit and urine pregnancy test to be performed prior to randomisation); 2. Run-in compliance to study drug and e-Diary completion <50% at randomisation; 3. History of “at risk” asthma: History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit which, in the judgement of the Investigator, may place the subject at undue risk; 4. Recent exacerbation: hospitalisation, emergency room admission or use of systemic corticosteroids for an asthma exacerbation in the 4 weeks prior to screening visit or during the run-in period; Note: Subjects experiencing an exacerbation during the run-in period may be re-screened once, at least 4 weeks after recovery. 5. Non-permanent asthma: exercise-induced, seasonal asthma (as the only asthma-related diagnosis) not requiring daily asthma control medicine; 6. Subjects using systemic corticosteroid medication in the 4 weeks or slow release corticosteroids in the 12 weeks, prior to screening; 7. Asthma requiring use of biologics: Subjects receiving asthma treatment with an injectable biologic drug such as monoclonal antibodies; 8. Respiratory disorders other than asthma: Subjects with known respiratory disorders other than asthma. This can include but is not limited to: diagnosis of COPD as defined by the current guidelines (e.g. GOLD Report), known a1-antitrypsine deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease; 9. Lung cancer or history of lung cancer: Subjects with an active diagnosis of lung cancer or a history of lung cancer; 10. Lung resection: Subjects with a history of lung volume resection; 11. Respiratory tract infection: Subjects with respiratory tract infection within 4 weeks prior to screening or during the run-in period;Note: Subjects experiencing a respiratory tract infection during the run-in period may be re-screened once, at least 4 weeks after recovery. 12. Smoking status: Current smoker or ex-smoker with a smoking history of =10 pack-years (pack-years = the number of cigarette packs per day times the number of years). Ex-smokers must have stopped smoking for =1 year (=6 months for e-cigarettes). 13. Cancer or history of cancer (other than lung): Subjects with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localised carcinoma (e.g. basal cell carcinoma, in situ carcinoma of the cervix adequately treated, …) is acceptable; 14. Cardiovascular diseases: Subjects who have clinically significant (CS) cardiovascular condition according to Investigator’s judgement, such as but not limited to: congestive heart failure (NYHA class IV), unstable or acute ischaemic heart disease in the last year prior to screening, history of sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months prior to screening (sustained meant lasting more than 30 seconds or ending only with external action, or led to haemodyn
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in pre-dose morning FEV1 at Week 26 in the study sub-population meeting PAL criterion at screening. The change from baseline in pre-dose morning FEV1 is measured by a pre-dose spirometry manoeuver done at V2 and V6 | — |
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects exhibiting on average NPAL - status over 26 weeks of treatment in the study sub-population meeting PAL criterion screening. 1. PAL status is measured by a Post-bronchodilator spirometry manoeuver at screening (within 30 minutes after inhaling 400 µg of salbutamol pMDI). 2. NPAL status is measured by a 2h post-dose spirometry manoeuvers from V2 to V6 | — |
Countries
Belgium, Bulgaria, England, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Netherlands, Northern Ireland, Poland, Slovakia, Spain, Sweden, United Kingdom, Wales
Outcome results
None listed