A 52 week study in which neither Sponsor or participant know the treatment assigned to subjects to compare the experimental drug (CHF 5993) with a commercial drug (Seretide® Evohaler®) in adolescent subjects with treated uncontrolled asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chiesi Farmaceutici S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Chiesi Farmaceutici S.p.a

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Efficacy

To demonstrate the superiority of CHF5993 BDP/FF/GB pMDI compared to Seretide® Evohaler® FP/SLM pMDI in terms of change from baseline in pre dose forced expiratory volume in the first second (FEV1) at Week 26.

Secondary objectives 10

1. To demonstrate the superiority of CHF5993 BDP/FF/GB pMDI compared to Seretide® Evohaler® FP/SLM pMDI in terms of change from baseline in 2 hour (h) post dose FEV1 at Week 26.
2. To compare the study treatments in terms of severe asthma exacerbations rate during the entire 52 weeks of treatment;
3. To compare the study treatments in terms of change from baseline in 7 item asthma control questionnaire (ACQ 7) and asthma quality of life questionnaire (AQLQ) at all the applicable visits;
4. To compare the study treatments in terms of change from baseline in pre dose FEV1 at all the applicable visits;
5. To compare the study treatments in terms of change from baseline in 2 h post-dose FEV1 at all the applicable visits;
6. To compare the study treatments in terms of 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);
7. To compare the study treatments in terms of change from baseline in 48 h post dose morning FEV1, after the last intake of study treatment at Week 52
8. To compare the study treatments in terms of change from baseline in weekly 5 item asthma control questionnaire (ACQ 5) over the entire 52 weeks of treatment
9. To compare the study treatments in terms of change from baseline in home spirometry parameters over the entire 52 weeks of treatment;
10. To assess the safety and the tolerability of the study treatments with respect to adverse events (AEs), electrocardiograms (ECGs), vital signs and laboratory tests during the entire 52 weeks of treatment.

Conditions and MedDRA coding

Uncontrolled Asthma

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001875-PIP02-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 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
2. Male or female patients aged ≥12 and <18 years
3. For the subset of subjects participating in the PK part of the study, body weight should be ≥30 kg
4. Subjects must have a documented history of asthma for at least 6 months
5. 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
6. 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
7. 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
8. Subjects with uncontrolled asthma evidenced by an ACQ-7 total score ≥1.5 at screening
9. 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
10. 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)

Exclusion criteria 25

1. Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake
2. Run-in treatment and e-diary compliance <50% at randomisation
3. 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;
4. 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
5. Any change in dose, schedule or formulation of the combination ICS plus LABA in the 4 weeks prior to Screening Visit (V1);
6. Subjects using SCS medication in the 4 weeks or slow-release corticosteroids in the 12 weeks, prior to screening
7. 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;
8. 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);
9. 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.
10. 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);
11. 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;
12. Subjects who received a vaccination within 2 weeks prior to screening or during the run-in
13. Subjects with a history of alcohol or drug abuse within 12 months prior to the start of the study
14. Subjects with known intolerance/hypersensitivity or contra indication to treatment with β2-agonists, ICS, anticholinergics or propellant gases/excipients
15. Subjects with major surgery in the 3 months prior to Screening Visit (V1) or planned surgery during the study
16. 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;
17. Subjects currently treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants
18. Subjects treated with monoclonal antibodies (e.g., anti immunoglobulin E or anti immunoglobulin G antibodies) or biological drugs
19. Subjects who are receiving any therapy that could interfere with the study treatments according to Investigator’s opinion
20. 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
21. Pregnant or lactating female subjects
22. Sexually active female subjects of childbearing potential not using a highly effective method of birth control
23. 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
24. Only for subjects included in the subset for PK assessment: Veins unsuitable for repeated venipuncture;
25. Only for subjects included in the subset for PK assessment:Blood donation or blood loss (>450 mL) in the 4 weeks before randomisation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in pre-dose FEV1 at Week 26

Secondary endpoints 15

1. Change from baseline in 2 h post-dose FEV1 at Week 26
2. Severe asthma exacerbation rate over the 52 weeks of treatment
3. Time to first severe exacerbation
4. Change from baseline in ACQ-7 at Week 12, Week 26 and Week 52 during study visits (using centralised spirometry);
5. Change from baseline in AQLQ at Week 12, Week 26 and Week 52
6. Change from baseline in pre-dose FEV1 at all clinical visits
7. Change from baseline in 2 h post-dose FEV1 at all clinical visits
8. 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);
9. Change from baseline in 48 h post-dose morning FEV1 after the last intake of study treatment at Week 52;
10. Change from baseline in weekly ACQ-5 over the 52 weeks of treatment
11. Change from baseline in home spirometry parameters over the 52 weeks of treatment
12. Occurrence of AEs and adverse drug reactions
13. Vital signs: change from baseline in systolic and diastolic blood pressure at all applicable visits
14. ECG parameters: change from baseline in heart rate, QTcF, PR interval and QRS interval at all applicable visits
15. Standard haematology and blood chemistry: change from baseline in standard haematology and blood chemistry parameters at all applicable visits

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chiesi Farmaceutici S.p.A.

Sponsor organisation

Chiesi Farmaceutici S.p.A.

Address

Via Palermo 26 A

City

Parma

Postcode

43122

Country

Italy

Scientific contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

Global Clinical Development

Public contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

Global Clinical Development

Third parties 10

Locations

3 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications