ASTHMA UNCONTROLLED ON MEDIUM DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG-ACTING ß2- AGONISTS MedDRA version: 22.1 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Chiesi Farmaceutici S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: MAIN Phase 1.Informed consent: Subject’s written informed consent obtained prior to any study related procedures; 2.Sex and age: Male or female subjects aged = 18 and = 75 years; 3.Diagnosis of asthma: A documented diagnosis of persistent 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, as described in GINA 2021 box 3-6) 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 prebronchodilator 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 asthma 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 willingness attitude and ability: - to correctly use the pMDI inhalers; - to perform all trial related procedures including technically acceptable pulmonary function tests; - to correctly use the e-Diary/e-Peak flow meter. 11.Female subjects: a.Woman of Childbearing Potential or b. Female patient of non-childbearing potential: Please refer to the protocol. OLE Phase 1. Informed consent: Subject´s written informed consent obtained prior to any study related procedures; 2. Participation in MiSTIC study main phase: Subjects enrolled in MiSTIC main phase, who did not discontinue from the main phase study treatment before Week 26 and with available data to allow classification into one of the two categories "Adequately Controlled Asthma" or "Uncontrolled Asthma" at the end of the main phase; 3. A willingness and ability: -To correctly use the pMDI inhalers; -To perform all trial related procedures including technically acceptable pulmonary function tests; -To correctly use the e-Diary; 4. Treatment compliance during main phase: Subjects with main phase study treatment compliance = 70% 5.Female subjects: a. Woman of Childbearing Potential or b. Female patient of non-childbearing potential: Please refer to the protocol 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 1000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: MAIN Phase 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 3 beats 2nd degree atrioventricular block t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): MAIN Phase Proportion of subjects exhibiting on average NPAL - status over 26 weeks of treatment in the study sub-population meeting PAL criterion at screening. OLE Phase Proportion of subjects with "Adequately Controlled Asthma" in the four afore mentioned cohorts of subjects (Cohort 1, 2, 3 and 4).;Timepoint(s) of evaluation of this end point: MAIN Phase: Over 26 weeks of treatment OLE Phase: Week 50;Main Objective: MAIN Phase To demonstrate the superiority of medium-dose BDP/FF/GB pMDI compared to high-dose BDP/FF pMDI in terms of the proportion of subjects exhibiting on average NPAL over 26 weeks of treatment in the study sub-population with PAL at screening. •A subject is defined as having PAL at screening if their post-bronchodilator (salbutamol) FEV1/FVC ratio is < 0.7. •A subject is defined as having NPAL during the treatment period if the mean of their 2h post-dose FEV1/FVC ratios collected during the 26-week treatment period is = 0.7. OLE Phase To assess the proportion of subjects whose asthma remains "Adequately Controlled": • on MS BDP/FF/GB at the end of the OLE phase in subjects with previously "Adequately Controlled Asthma" (Cohort 1 on HS BDP/FF, Cohort 4 on MS BDP/FF/GB) • on HS BDP/FF/GB at end of the OLE phase in subjects with previously "Uncontrolled Asthma"(Cohort 2 on MS BDP/FF/GB, cohort 3 on HS BDP/FF) at the end of the main phase.;Secondary Objective: To demonstrate the superiority of medium-dose BDP/FF/GB pMDI (100/6/12.5 µg, 2 puffs bid) compared to high dose BDP/FF pMDI (200/6 µg, 2 puffs bid) in terms of change from baseline in pre-dose FEV1 at Week 26 in the study sub-population meeting PAL criterion at screening. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): MAIN Phase only: Change from baseline in pre-dose morning FEV1 at Week 26 in the study sub-population meeting PAL criterion at screening.;Timepoint(s) of evaluation of this end point: MAIN Phase only: From baseline to week 26 | — |
Countries
Belgium, Bulgaria, Czechia, Czech Republic, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Netherlands, Poland, Slovakia, Spain, Sweden, United Kingdom
Contacts
Public ContactCLINICAL PROJECT MANAGER
Chiesi Farmaceutici S.p.A.
Outcome results
None listed