A comparison study between adolescents with asthma and adults with asthma on how they absorb, metabolise and eliminate CHF 6001

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chiesi Farmaceutici S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

24 Mar 2025 → 11 Aug 2025

Decision date (initial)

2025-01-23

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: Pharmacokinetic, Safety, Pharmacodynamic

To evaluate the PK profile of CHF 6001 after oral inhalation of CHF 6001 3200 μg with NEXThaler® device in adolescent subjects with asthma in comparison to adult subjects with asthma.

Secondary objectives 2

1. To evaluate the systemic effects in terms of heart rate (HR) and also the general safety and tolerability profile of CHF 6001 in adolescent and adult subjects with asthma.
2. To evaluate the PK profile of metabolites of CHF 6001, CHF 5956 and CHF 6095, after oral inhalation of CHF 6001 3200 μg with NEXThaler® device in adolescent subjects with asthma in comparison to adult subjects with asthma.

Conditions and MedDRA coding

Asthma

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003393-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Informed consent: subject’s and/or parents or legal representative (for adolescents) written informed consent obtained prior to any study-related procedures.
2. Sex and age: a. Adolescent: male or female subjects aged ≥12 and <18 years; b. Adult: male or female subjects aged ≥18 and ≤75 years;
3. Body weight for adolescents within the range of ≥19 kg for 12 years old and ≥30 kg for 13 to 17 years old.
4. Body mass index for adults within the range of ≥18.0 to ≤30.0 kg/m2.
5. Diagnosis of asthma: a documented history of physician diagnosed asthma according to international guidelines GINA update 2024 for ≥1 year, with diagnosis before the age of 50 years for adults.
6. Stable asthma therapy: a stable treatment with medium dose of ICS (medium-dose ICS defined as beclometasone dipropionate [BDP] non-extrafine >500 to 1000 μg or estimated clinical comparable dose as per GINA guidelines update 2024) alone or in fixed combination with a LABA with or without long-acting muscarinic antagonist (for subjects ≥18 years old only) for ≥3 months before screening.
7. Lung function: adolescent and adult subjects with a FEV1 >70% of predicted values (% predicted) after withholding short-acting β2-agonist (SABA) treatment for a minimum of 6 hours before screening or 24 hours in case of ICS and LABA (alone or in fixed combination).
8. A cooperative attitude and ability: a. To correctly use the inhalers; b. To perform all study-related procedures including technically acceptable spirometry according to the 2019 American Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines.
9. Female subjects fulfilling one of the following criteria: a. Women of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e., postmenopausal or permanently sterile, as per definitions given in APPENDIX 4 of the Protocol and Section 1.1 of the Clinical Trials Coordination Group (CTCG) guidance). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per Investigator’s request, postmenopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges). b. Women of childbearing potential (WOCBP) fulfilling one of the following criteria: i. 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 (FU) visit or; ii. WOCBP with non-fertile male partners (contraception is not required in this case). For the definition of WOCBP, fertile men and the list of highly effective birth control methods, refer to APPENDIX 4 of the Protocol (or Section 1.1 and 4.1 of the CTCG guidance).

Exclusion criteria 23

1. Blood donation (≥450 mL) or blood loss, less than 2 months before screening or before enrolment on Day 1, applicable for adults only.
2. 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.
3. Recent exacerbation or respiratory tract infection: hospitalisation, emergency room admission or use of systemic corticosteroids for an asthma exacerbation or respiratory tract infection in the 4 weeks before the screening visit. Note: Subjects experiencing an exacerbation or respiratory tract infection during the screening visit may be rescreened once, ≥6 weeks after recovery. If there is no recovery, such event constitutes an exclusion criterion and leads to screening failure.
4. Subjects using systemic corticosteroid medication 4 weeks or slow-release corticosteroids 12 weeks before enrolment.
5. Subjects being treated with anti-inflammatory asthma monoclonal antibodies or biological drugs which can affect asthma inflammation within 6 months before or five half-lives (whichever is greater) before the screening visit.
6. Respiratory disorders other than asthma: subjects with known respiratory disorders other than asthma. This can include, but is not limited to, COPD, α1-antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease and others.
7. Smoking status: current smoker, ex-smoker with a smoking history of ≥10 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 for ≥1 year (≥6 months for e-cigarettes).
8. Alcohol/drug abuse: subjects with a known or suspected history of alcohol and/or drug abuse within 12 months before screening.
9. Cancer or history of cancer: subjects with active cancer or a history of cancer with <5 years disease free survival time (whether 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.
10. Cardiovascular disease: subjects who have CS cardiovascular condition according to Investigator’s judgement, such as heart failure (New York Heart Association class >3), acute ischemic heart disease in the last year prior to screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months prior to screening (sustained means lasting >30 seconds or ending only with external action, or leads to haemodynamic collapse; nonsustained means >3 beats <30 seconds, and/or ending spontaneously and/or asymptomatic), high degree impulse conduction blocks (>2nd degree atrioventricular block type 2). Similarly, subjects affected by persistent, long-standing or paroxysmal atrial fibrillation will not be considered for enrolment. Note: Subjects with permanent atrial fibrillation (for ≥6 months before the screening visit) with a resting ventricular rate <100/min, controlled with a rate control strategy (i.e., selective β-blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) can be considered for enrolment.
11. Electrocardiogram criteria: an abnormal and CS 12-lead ECG that in the Investigator's opinion would affect efficacy or safety evaluation or place the subjects at risk. Male subjects whose 12-lead ECG shows QTcF >450 ms or female subjects with a QTcF >460 ms (adolescent females) or >470 ms (adult females) at screening or at enrolment (criterion not applicable for subjects with pacemaker or permanent atrial fibrillation).
12. Other severe acute or chronic medical 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.
13. Liver diseases: subjects with severe hepatitis, chronic active hepatitis or evidence of uncontrolled chronic liver disease according to the Investigator’s opinion.
14. Drugs with hepatoxicity potential: subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (i.e., isoniazide, nimesulide, ketoconazole) and strong inhibitors of cytochrome P450 (CYP) 3A4/5 (i.e., itraconazole) within the previous 3 months before the screening visit.
15. Subjects having received a vaccination within 2 weeks before the screening visit.
16. Subjects with major surgery in the 3 months before the screening visit or planned surgery during the study.
17. Subjects with a history of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study.
18. Subjects treated with monoamine oxidase inhibitors or tricyclic antidepressants.
19. Subjects treated with non-potassium sparing diuretics (unless administered as a fixed dose combination with a potassium conserving drug or changed to potassium sparing agent before the screening), non-selective beta blocking drugs, quinidine, quinidine-like anti-arrhythmics or any medication with a QTc prolongation potential or a history of QTc prolongation.
20. Subjects who are receiving any therapy that could interfere with the study treatments according to Investigator’s opinion.
21. Subjects who have received an investigational drug within 30 days or five half-lives (whichever is greater) prior to the screening visit, or have been previously enrolled in this study or are currently participating in another study.
22. Documented coronavirus disease 2019 diagnosis within the last 2 weeks, or associated complications or symptoms, which have not resolved within 14 days before screening.
23. For females only: pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until termination of the gestation, confirmed by a positive serum human chorionic gonadotropin laboratory test at SCR visit and urine test at Day 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CHF 6001 Cmax and area under the curve from 0 to the last quantifiable concentration (AUC 0-t).

Secondary endpoints 3

1. PK variables will be evaluated after oral inhalation of CHF 6001 3200 μg with NEXThaler® device: • For CHF 6001: apparent systemic clearance (CL/F), time to maximum plasma concentration (tmax), area under the curve from 0 to infinity (AUC0-∞) and elimination half-life (t1/2); • For CHF 5956 and CHF 6095: tmax, AUC0-∞ and apparent terminal t1/2, Cmax and AUC0-t;
2. PD variables will be evaluated at different times from pre-dose until 10 hours post-dose: • Triplicate 12-lead ECG parameters: HR (including average 0 to 4 hours and 0 to 10 hours) and PR and QRS intervals and QTcF; • Systolic and diastolic BP.
3. Determination of the safety profile will be based on the following assessments at different times from pre-dose until Visit 4 (follow-up visit): • AEs and adverse drug reactions (ADRs); • Standard laboratory parameters (haematology and blood chemistry; at screening and when clinically indicated); • HR from local 12-lead safety ECG (measured during visits); • BP (measured during visits).

Investigational products

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

Test 1

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 4

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 28 files

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

Application history

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