A Study Testing the Superiority of CHF 1535 pMDI 800/24µg Total Daily Dose Compared With CHF 718 pMDI 800µg Total Daily Dose in Adults With Asthma on Medium or High-Dose Inhaled Corticosteroid

Phase 3

Completed

• Conditions: Asthma
• Interventions: Drug: Beclomethasone Dipropionate/Formoterol Fumarate; Drug: Beclomethasone Dipropionate

• Registration Number: NCT05292586
• Lead Sponsor: Chiesi Farmaceutici S.p.A.

Brief Summary

Compare the superiority of CHF 1535 versus CHF 718 in subjects with asthma who are on medium or high dose inhaled corticosteroids.

Detailed Description

This was a phase III, multicenter, randomized, double-blind active controlled 2-arm parallel group to compare superiority of CHF 1535 pressurised metered dose inhaler (pMDI) compared with CHF 718 pMDI, in subjects with asthma on medium or high dose inhaled corticosteroids, with regard to change from baseline in forced expiratory volume in the first second (FEV1) Area under the Curve Calculated Between Time 0 and 12 Hours (AUC0-12h) at Week 12.

After screening, eligible subjects entered a 2-week run-in period using CHF 718 (BDP) pMDI 100µg, followed by a 12-week double-blind, treatment period. Screened subjects who were on a medium dose inhaled corticosteroid (ICS) or medium dose ICS-long-acting β2-adrenergic receptor agonists (LABA) prior to the study, received CHF 718 pMDI 100µg 2 inhalations twice daily (BID) i.e. total daily dose (TDD) 400µg) during the 2-week run in period. Screened subjects who were on a high dose ICS prior to the study received CHF 718 pMDI 100µg 4 inhalations BID (TDD 800µg) during the 2-week run in period.

Following the run-in period, eligible subjects were randomized to one of two study drug arms (using a 1:1 allocation ratio) for 12 weeks. A total of 6 clinic visits (V), (V0-V5) and a follow-up call (V6) were performed during the study.

During the study, daily symptoms, rescue medication use, and compliance with the study drug were recorded via a subject-specific electronic diary (eDiary). Concomitant medications and adverse events (AEs) were assessed and recorded throughout the study. Vital signs measurements, physical exam, 12-lead electrocardiogram (ECG), peak expiratory flow (PEF), and spirometry measurements, including serial spirometry were performed and recorded. Symptoms were assessed using disease specific questionnaires. Routine hematology, blood chemistry, and urine pregnancy testing were performed before enrolment and at the end of study.

CHF 1535 pMDI = 200/6 μg pressurised metered dose inhaler (fixed combination of extrafine beclomethasone dipropionate \[BDP\] plus formoterol fumarate \[FF\]).

CHF 718 pMDI = 100 μg pressurised metered dose inhaler (extrafine beclomethasone dipropionate \[BDP\]).

Study Timeline

• Study First Submitted: 2022-03-04
• Study First Submitted QC: 2022-03-14
• Study First Posted: 2022-03-23
• Study Start: 2022-08-31
• Primary Completion: 2024-06-24
• Study Completion: 2024-06-24
• Results First Submitted: 2025-06-23
• Status Verified: 2025-09
• Results First Submitted QC: 2025-09-02
• Last Update Submitted: 2025-09-02
• Results First Posted: 2025-09-04
• Last Update Posted: 2025-09-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1377

Inclusion Criteria

Not provided

Exclusion Criteria

1. Pregnancy or lactation: 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 and urine pregnancy test to be performed at screening visit and urine pregnancy test to be performed prior to randomization).
2. Poor compliance with run-in medication or eDiary completion <50% before randomization.
3. History of "at risk" asthma: History of near-fatal asthma or of a past hospitalization for asthma in intensive care unit which, in the judgement of the investigator, may place the subject at undue risk.
4. Recent asthma exacerbation: Hospitalization, 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.
5. Unresolved respiratory tract infection (RTI) in the 4 weeks prior to the screening visit or during run-in period. Documented coronavirus disease 2019 (COVID-19) diagnosis within the last 8 weeks or complications from this disease, which have not resolved within 14 days prior to screening.
6. Unstable ICS dose during the 4 weeks prior to screening visit, including any change in dose, schedule, or formulation.
7. Use of systemic corticosteroid medication in the 4 weeks prior to screening or slow-release corticosteroids in the 12 weeks before screening.
8. Respiratory disorders other than asthma: History of a diagnosis of cystic fibrosis, bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), (as defined by the current Global Initiative for Chronic Obstructive Lung Disease [GOLD] Report), alpha-1 antitrypsin deficiency, or any other significant lung disease which may interfere with study evaluations.
9. Smoking status: Current smokers or ex-smokers with total cumulative exposure equal to or more than 10 pack-years or having stopped smoking within one year prior to screening visit.
10. E-cigarette status: Current e-cigarettes users at the time of the screening visit.
11. Cannabis usage: Current use of inhaled or oral cannabis products (e.g. marijuana).
12. Substance abuse: Subjects with a history of alcohol or substance/drug abuse within 12 months prior to screening.
13. Cardiovascular diseases: Subjects who have clinically significant cardiovascular condition such as, but not limited to, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV heart failure, acute ischemic heart disease within one year prior to study entry, known history of atrial fibrillation or history of sustained and non-sustained cardiac arrhythmias diagnosed within the last 6 months prior to screening, not controlled with a rate control strategy. Note: Subjects with Permanent Atrial Fibrillation (for at least 6 months) 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 the enrollment.
14. ECG criteria: An abnormal and clinically significant 12-lead electrocardiogram (ECG) which may impact the safety of the subject according to Investigator's judgement. In terms of the QTcF, subjects with QTcF >450ms for males or QTcF >470ms for females at screening or at randomization visits (criterion not applicable for subject with pacemaker or permanent atrial fibrillation).
15. Other medical conditions: Other active severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug 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.
16. Vaccination: Subjects having received a vaccination within 2 weeks prior to screening or during the run-in period.
17. Subjects' wellbeing: Subjects mentally or legally incapacitated, including but not limited to subjects who are institutionalized or incarcerated.
18. Hypersensitivity: Subjects with known intolerance, hypersensitivity or contraindication to treatment with ß2-agonists, ICS, or propellant gases/excipients.
19. Surgery: Subjects with major surgery in the 3 months prior to the screening visit or planned surgery during the study.
20. Additional treatment: 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-arrhythmic, or any medication with a QTc prolongation potential or a history of QTc prolongation.
21. Subjects treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants.
22. Subjects with concomitant immunosuppressive therapy, use of oral or injected corticosteroids, anti-immunoglobulin E (IgE), anti-IL5 or other monoclonal or polyclonal antibodies within 12 weeks prior to screening.
23. Subjects who are receiving any therapy that could interfere with the study drugs according to investigator's opinion.
24. Participating in other investigational trial: Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
25. Spacer: The need to use a spacer for correct self-administration of a pMDI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CHF 1535 pMDI	Beclomethasone Dipropionate/Formoterol Fumarate	CHF 1535 pMDI 800/24µg TDD
CHF 718 pMDI	Beclomethasone Dipropionate	CHF 718 pMDI 800µg TDD

Primary Outcome Measures

Name	Time	Method
1_Change From Baseline in FEV1 AUC0-12h Normalised by Time at Week 12	Baseline (pre-dose on Week 0) and Week 12.	The pre-dose FEV1 at baseline (i.e. pre-dose on Week 0 \[Visit 2\]) and the FEV1 AUC0-12h normalised by time at Week 12 (Visit 5) are presented by treatment group in the ITT population, as change from baseline.; AUC0=12h Area under the curve calculated between time 0 and 12 hours

Secondary Outcome Measures

Name	Time	Method
2_Change From Baseline in Peak FEV1 Within the First 3 Hours Post-dose at Week 12	Baseline (pre-dose on Week 0) and Week 12.	The peak FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the peak FEV1 within the first 3 hours post-dose at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline.; FEV1=Forced Expiratory Volume in the First Second
3_Change From Baseline in FEV1 AUC0-12h Normalised by Time at Week 0	Baseline (pre-dose on Week 0) and Week 12.	The pre-dose FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the FEV1 AUC0-12h normalised by time at Week 0 (V2, post-dose) are presented by treatment group in the ITT population, as change from baseline.
4_Change From Baseline in Peak FEV1 Within the First 3 Hours Post-dose at Week 0	Baseline (pre-dose on Week 0) and 3 h post dose on Week 0.	The peak FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the peak FEV1 within the first 3 hours post-dose at Week 0 (V2, post-dose) are presented by treatment group in the ITT population, as change from baseline.; FEV1=Forced Expiratory Volume in the First Second
5_Change From Baseline in Trough FEV1 at Week 12	Baseline (pre-dose on Week 0) and Week 12.	The trough FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]), the trough FEV1 at Week 12 (V5) and the change from baseline in trough FEV1 at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline.; FEV1=Forced Expiratory Volume in the First Second
6_Change From Baseline in Pre-dose Morning FEV1 at Weeks 4, 8 and 12	Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.	The pre-dose MORNING FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the pre-dose morning FEV1 at Week 4 (V3), Week 8 (V4) and Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline.; FEV1=Forced Expiratory Volume in the First Second
7_Proportion of Pre-dose Morning FEV1 Responders at Weeks 4, 8 and 12	Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.	The proportion of pre-dose MORNING FEV1 responders at Week 4 (V3), Week 8 (V4) and Week 12 (V5) are presented by treatment group in the ITT population. The proportion of subjects classified as pre-dose morning FEV1 responders (i.e. those subjects who had change from baseline in pre-dose morning FEV1 ≥100 mL).; FEV1=Forced Expiratory Volume in the First Second
8_Proportion of Trough FEV1 Responders at Week 12	Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.	The proportion of trough FEV1 responders at Week 12 (V5) are presented by treatment group in the ITT population.; The proportion of subjects classified as trough FEV1 responders (i.e. those subjects who had change from baseline in trough FEV1 ≥100 mL).; FEV1=Forced Expiratory Volume in the First Second
9_Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period	Baseline (Week 0) to Week 12.	The average MORNING PEF at baseline (i.e. average morning "Best PEF" values during the run-in period, over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population), as change from baseline.; PEF=Peak Expiratory Flow
10_Change From Baseline in Average Evening Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period	Baseline (Week 0) to Week 12.	The average EVENING PEF at baseline (i.e. average evening "Best PEF" values during the run-in period, see Section 9.7.1.4), over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline.; PEF=Peak Expiratory Flow
11_Change From Baseline in ACQ-7 Score and ACQ-5 Score at Week 12	Baseline (pre-dose on Week 0) and Week 12.	The ACQ-7 and ACQ-5 scores at baseline (i.e. pre-dose on Week 0 \[V2\]) and at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline; only patients who provided required data at baseline and at specified times are included in the calculation.; Asthma control was evaluated during the treatment period (Week 0 to Week 12 \[V2-V5\])/end of treatment (ET) if applicable, using ACQ-7; first 6 items refer to symptoms and rescue use in the previous 7 days. The 7th item, filled in by the clinical staff, was the FEV1 (% predicted) recorded at 15 min pre-dose, measured at each visit during the treatment period. ACQ-5 has 5 items on adequacy of asthma control.; ACQ-7: Assess asthma symptoms over last 7 days (night-time awakenings due to symptoms, morning symptoms, activity limitation, shortness of breath, wheezing), average daily rescue medication use, and current FEV1 percent predicted. Score scale: 0=totally controlled; 6=severely uncontrolled.
12_Change From Baseline in Percentage of Rescue Medication-free Days Over the 12-Week Treatment Period	Baseline (pre-dose on Week 0) and Week 12.	The percentage of rescue medication-free days at baseline (i.e. percentage of days during the run-in period with no rescue medication), over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline.
13_Change From Baseline in Percentage of Asthma Symptom-free Days Over the 12-Week Treatment Period	Baseline (pre-dose on Week 0) and Week 12.	The percentage of asthma symptom-free days at baseline (i.e. percentage of days during the run-in period with no asthma symptom, over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline.

Trial Locations

Locations (91)

Chiesi Clinical Trial Site 840858; 🇺🇸 Mobile, Alabama, United States

Chiesi Clinical Trial Site 840895; 🇺🇸 Chandler, Arizona, United States

Chiesi Clinical Trial Site 840856; 🇺🇸 Encinitas, California, United States

Chiesi Clinical Trial Site 840843; 🇺🇸 Huntington Beach, California, United States

Chiesi Clinical Trial Site 840860; 🇺🇸 Huntington Beach, California, United States

Chiesi Clinical Trial Site 840896; 🇺🇸 Long Beach, California, United States

Chiesi Clinical Trial Site 840883; 🇺🇸 Los Angeles, California, United States

Chiesi Clinical Trial Site 840810; 🇺🇸 Los Angeles, California, United States

Chiesi Clinical Trial Site 840869; 🇺🇸 Newport Beach, California, United States

Chiesi Clinical Trial Site 840890; 🇺🇸 North Hollywood, California, United States

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