Glycopyrronium bromide; Formoterol fumarate dihydrate; Beclometasone dipropionate anhydrous for Asthma | Uncontrolled asthma

Inclusion criteria

• {"criterion_text":"- Written informed consent obtained from the parents/legal representatives (according to the local regulation) and written or verbal assent by the subject (when appropriate), obtained prior to any study-related procedures"}
• {"criterion_text":"- A cooperative attitude and ability to: a)Be trained to correctly use the pMDI inhalers and the spacer, if applicable; b)Perform all study related procedures including technically acceptable pulmonary function tests and home spirometry; c)Correctly use the electronic diary (e-Diary)"}
• {"criterion_text":"- Male or female patients aged ≥12 and <18 years"}
• {"criterion_text":"- For the subset of subjects participating in the PK part of the study, body weight should be ≥30 kg"}
• {"criterion_text":"- Subjects must have a documented history of asthma for at least 6 months"}
• {"criterion_text":"- Subjects in treatment with double therapy with medium doses of ICS in fixed or free combination with a LABA (>500 1000 µg daily dose BDP non extrafine or estimated clinically comparable dose plus formoterol 24 µg/day or salmeterol 100 µg/day or vilanterol 25 µg/day) at a stable dose for at least 4 weeks prior to screening"}
• {"criterion_text":"- Subjects with a pre-BD FEV1 ≤90% and ≥60% of their predicted normal value, after appropriate washout from BDs, at the Screening and Randomisation Visits"}
• {"criterion_text":"- Subjects with a positive response to a reversibility test at screening, defined as ΔFEV1 ≥12% and ≥200 mL over baseline, 10 to 15 minutes (min) after inhaling 200-400 µg of salbutamol pMDI"}
• {"criterion_text":"- Subjects with uncontrolled asthma evidenced by an ACQ-7 total score ≥1.5 at screening"}
• {"criterion_text":"- A documented history of one or more asthma exacerbations requiring treatment with systemic corticosteroids (SCS) or emergency department visit or in-patient hospitalisation in the previous 12 months"}

Exclusion criteria

• {"criterion_text":"- Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake"}
• {"criterion_text":"- Run-in treatment and e-diary compliance <50% at randomisation"}
• {"criterion_text":"- History of “at risk” asthma: history of near fatal asthma or of a past hospitalisation for asthma in an intensive care unit which, in the judgement of the Investigator, may place the subject at undue risk;"}
• {"criterion_text":"- Recent exacerbation or respiratory tract infection: hospitalisation, emergency room admission or use of SCS for an asthma exacerbation or a documented diagnosis of lower respiratory tract infection that required antibiotics or an unresolved respiratory tract infection within 4 weeks prior to Screening Visit (V1) or during the run-in period"}
• {"criterion_text":"- Any change in dose, schedule or formulation of the combination ICS plus LABA in the 4 weeks prior to Screening Visit (V1);"}
• {"criterion_text":"- Subjects using SCS medication in the 4 weeks or slow-release corticosteroids in the 12 weeks, prior to screening"}
• {"criterion_text":"- Respiratory disorders other than asthma: this can include but is not limited to: α1-antitrypsin deficiency, active tuberculosis, bronchiectasis, cystic fibrosis, sarcoidosis, pulmonary hypertension and interstitial lung disease;"}
• {"criterion_text":"- Current smokers (including e-cigarettes, vaping and hookah), or ex-smokers with a smoking history of ≥5 pack-years (pack-years = the number of cigarette packs per day times the number of years), or current use of inhaled or oral cannabis products. Ex-smokers must have stopped smoking ≥1 year (≥6 months for e-cigarettes);"}
• {"criterion_text":"- Cardiovascular diseases: subjects who have clinically significant (CS) cardiovascular condition according to the Investigator’s judgement, such as but not limited to: congenital heart abnormality, congestive heart failure (New York Heart Association class >3), history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds or ending only with external action, or leads to haemodynamic collapse; non-sustained means >3 beats <30 seconds, and or ending spontaneously, and or asymptomatic), high degree impulse conduction blocks (>2nd degree atrioventricular block type 2), subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction, ischaemic heart disease, occlusive vascular diseases, arterial hypertension and aneurysm. Similarly, subjects affected by persistent, long standing or paroxysmal atrial fibrillation or supraventricular tachycardia will not be considered for enrolment."}
• {"criterion_text":"- ECG criteria: any abnormal and CS 12 lead ECG in the Investigator’s opinion that would affect efficacy or safety evaluation or place the subjects at risk. Subjects whose 12 lead ECG shows QT interval corrected using Fridericia’s formula (QTcF) >440 msec for males or QTcF >460 msec for females at Screening or at Randomisation Visits (criterion not applicable for subjects with pacemaker or permanent atrial fibrillation);"}
• {"criterion_text":"- Other severe acute or chronic medical (such as but not limited to thyrotoxicosis, diabetes mellitus, and untreated hypokalaemia) or malignancy or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study;"}
• {"criterion_text":"- Subjects who received a vaccination within 2 weeks prior to screening or during the run-in"}
• {"criterion_text":"- Subjects with a history of alcohol or drug abuse within 12 months prior to the start of the study"}
• {"criterion_text":"- Subjects with known intolerance/hypersensitivity or contra indication to treatment with β2-agonists, ICS, anticholinergics or propellant gases/excipients"}
• {"criterion_text":"- Subjects with major surgery in the 3 months prior to Screening Visit (V1) or planned surgery during the study"}
• {"criterion_text":"- Subjects treated with non-potassium sparing diuretics (unless administered as a fixed-dose combination with a potassium conserving drug or changed to potassium sparing before the screening), non-selective beta-blocking drugs, quinidine, quinidine like anti-arrhythmics, or any medication with a QT interval corrected for heart rate (QTc) prolongation potential within the last 2 weeks prior to screening, or a history of QTc prolongation;"}
• {"criterion_text":"- Subjects currently treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants"}
• {"criterion_text":"- Subjects treated with monoclonal antibodies (e.g., anti immunoglobulin E or anti immunoglobulin G antibodies) or biological drugs"}
• {"criterion_text":"- Subjects who are receiving any therapy that could interfere with the study treatments according to Investigator’s opinion"}
• {"criterion_text":"- Documented coronavirus disease 2019 (COVID-19) diagnosis within the last 2 weeks, or associated complications/symptoms, which have not resolved within 14 days prior to screening or randomisation"}
• {"criterion_text":"- Pregnant or lactating female subjects"}
• {"criterion_text":"- Sexually active female subjects of childbearing potential not using a highly effective method of birth control"}
• {"criterion_text":"- Subjects who have received an investigational drug within 2 months or six half-lives (whichever is greater) prior to Screening Visit (V1), or have been previously randomised in this study, or are currently participating in another clinical study"}
• {"criterion_text":"- Only for subjects included in the subset for PK assessment: Veins unsuitable for repeated venipuncture;"}
• {"criterion_text":"- Only for subjects included in the subset for PK assessment:Blood donation or blood loss (>450 mL) in the 4 weeks before randomisation"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in pre-dose FEV1 at Week 26","definition_or_measurement_approach":"Change from baseline in pre-dose forced expiratory volume in the first second (FEV1) at Week 26."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in 2 h post-dose FEV1 at Week 26","definition_or_measurement_approach":"Change from baseline in FEV1 measured 2 hours post-dose at Week 26."}
• {"endpoint_text":"- Severe asthma exacerbation rate over the 52 weeks of treatment","definition_or_measurement_approach":"Rate of severe asthma exacerbations during the 52 weeks of treatment."}
• {"endpoint_text":"- Time to first severe exacerbation","definition_or_measurement_approach":"Time (duration) from randomisation to first severe asthma exacerbation."}
• {"endpoint_text":"- Change from baseline in ACQ-7 at Week 12, Week 26 and Week 52 during study visits (using centralised spirometry);","definition_or_measurement_approach":"Change from baseline in 7-item Asthma Control Questionnaire (ACQ-7) at Weeks 12, 26 and 52; centralised spirometry referenced in the endpoint description."}
• {"endpoint_text":"- Change from baseline in AQLQ at Week 12, Week 26 and Week 52","definition_or_measurement_approach":"Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) at Weeks 12, 26 and 52."}
• {"endpoint_text":"- Change from baseline in pre-dose FEV1 at all clinical visits","definition_or_measurement_approach":"Change from baseline in pre-dose FEV1 assessed at each clinical visit."}
• {"endpoint_text":"- Change from baseline in 2 h post-dose FEV1 at all clinical visits","definition_or_measurement_approach":"Change from baseline in 2-hour post-dose FEV1 assessed at all clinical visits."}
• {"endpoint_text":"- Proportion of subjects classified as responders in terms of pre dose FEV1 at Week 26 and Week 52 (i.e., subjects with change from baseline in pre-dose FEV1 ≥100 mL);","definition_or_measurement_approach":"Proportion of subjects with pre-dose FEV1 change from baseline ≥100 mL at Weeks 26 and 52."}
• {"endpoint_text":"- Change from baseline in 48 h post-dose morning FEV1 after the last intake of study treatment at Week 52;","definition_or_measurement_approach":"Change from baseline in morning FEV1 measured 48 hours post-dose after the last intake of study treatment at Week 52."}
• {"endpoint_text":"- Change from baseline in weekly ACQ-5 over the 52 weeks of treatment","definition_or_measurement_approach":"Change from baseline in weekly 5-item Asthma Control Questionnaire (ACQ-5) across the 52-week treatment period."}
• {"endpoint_text":"- Change from baseline in home spirometry parameters over the 52 weeks of treatment","definition_or_measurement_approach":"Change from baseline in home spirometry parameters recorded over the 52-week treatment period."}
• {"endpoint_text":"- Occurrence of AEs and adverse drug reactions","definition_or_measurement_approach":"Occurrence and reporting of adverse events (AEs) and adverse drug reactions throughout the study; safety assessed by AEs, ECGs, vital signs and laboratory tests as per secondary objectives."}
• {"endpoint_text":"- Vital signs: change from baseline in systolic and diastolic blood pressure at all applicable visits","definition_or_measurement_approach":"Change from baseline in systolic and diastolic blood pressure measured at applicable visits."}
• {"endpoint_text":"- ECG parameters: change from baseline in heart rate, QTcF, PR interval and QRS interval at all applicable visits","definition_or_measurement_approach":"Change from baseline in ECG parameters including heart rate, QTcF, PR interval and QRS interval at applicable visits."}
• {"endpoint_text":"- Standard haematology and blood chemistry: change from baseline in standard haematology and blood chemistry parameters at all applicable visits","definition_or_measurement_approach":"Change from baseline in standard haematology and blood chemistry laboratory parameters at applicable visits."}

Methods

• Use of site-based recruitment through participating hospitals/clinics listed in Part II (Germany, Italy, Spain).
• Use of the Studienproband website for recruitment material (explicit document: 'K2_Recruitment material using Studienproband website').
• Direct To Patient (DtP) management for patient-related activities (documented responsibility: Marken Italy s.r.l. — 'Management of the Direct To Patient (DtP)').
• Local recruitment arrangements documented per Member State (K1_Recruitment arrangements documents for Germany, Italy and Spain exist).

Germany

Earliest CTIS Part Ii Submission Date

14-08-2025

Latest Decision Or Authorization Date

26-09-2025

Processing Time Days

43

Number Of Sites

3

Number Of Participants

67

Italy

Earliest CTIS Part Ii Submission Date

07-07-2025

Latest Decision Or Authorization Date

29-09-2025

Processing Time Days

84

Number Of Sites

12

Number Of Participants

40

Spain

Earliest CTIS Part Ii Submission Date

22-08-2025

Latest Decision Or Authorization Date

30-09-2025

Processing Time Days

39

Number Of Sites

9

Number Of Participants

40

Primary sponsor

Full Name

Chiesi Farmaceutici S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Icon (Lr) Limited

Responsibilities

codes 10,6

Name

Almac Clinical Services Limited

Responsibilities

code 14

Name

Clinchoice S.r.l.

Responsibilities

codes 1,12,13,14,2,5,8,9

Name

eResearchTechnology GmbH

Responsibilities

Home Spirometry, Central Spirometry, ECG

Name

Almac Group Limited

Responsibilities

code 3

Name

SGS Belgium

Responsibilities

code 4

Third parties

• {"country":"Belgium","full_name":"SGS Belgium","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Group Limited","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Clinchoice S.r.l.","duties_or_roles":"codes 1,12,13,14,2,5,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code 15 (eCoA)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"code 15 (Patient Reimbursment (where applicable))","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Marken Italy s.r.l.","duties_or_roles":"code 15 (Management of the Direct To Patient (DtP))","organisation_type":"Industry"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"code 15 (Home Spirometry, Central Spirometry, ECG)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"codes 10,6","organisation_type":"Non-Pharmaceutical company"}