Clinical trial NCT05292586: A Study Testing the Superiority of CHF 1535 pMDI 800/24µg Total Daily Dose Compared to CHF 718 pMDI 800µg Total Daily Dose in Adults With Asthma on Medium or High-Dose Inhaled Corticosteroid
Official title: A 12 Week, Randomized, Double-blind, Multicenter, Active Controlled, 2-Arm Parallel Group Study Testing the Superiority of CHF 1535 pMDI 800/24µg Total Daily Dose (Fixed Combination of Extrafine Beclomethasone Dipropionate Plus Formoterol Fumarate) Compared to CHF 718 pMDI 800µg Total Daily Dose (Extrafine Beclomethasone Dipropionate) in Adults With Asthma on Medium or High-Dose Inhaled Corticosteroid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Beclomethasone Dipropionate
Beclometasone dipropionate/Formoterol fumarate
Inhaled Corticosteroids
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2022-03-23
Enrollment: 1377
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the superiority of CHF 1535 compared to CHF 718 in subjects with asthma on medium or high dose inhaled corticosteroids.

Detailed description: This is a phase III, multicenter, randomized, double-blind active controlled 2-arm parallel group to compare superiority of CHF 1535 pMDI compared to CHF 718 pMDI in terms of change from baseline in FEV1 AUC0-12h at Week 12.

After screening, eligible subjects will enter 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 ICS or medium dose ICS-LABA prior to the study will be put on CHF 718 pMDI 100µg 2 inhalations BID (TDD 400µg) during the 2-week run in period. Screened subjects who were on a high dose ICS prior to the study will be put on CHF 718 pMDI 100µg 4 inhalations BID (TDD 800µg) during the 2-week run in period.

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

During the study, daily symptoms, rescue medication use and compliance with the study drug will be recorded via a subject electronic diary. Subject concomitant medications, and adverse events will be assessed and recorded throughout the study. At study visits, subjects will undergo vital signs, physical exam, 12-lead ECG, PEF, and spirometry measurements, including serial spirometry at V2 and V5. Symptoms will be assessed through disease specific questionnaires. Routine hematology, blood chemistry, and serum pregnancy testing will be performed before enrollment and at end of study.

Eligibility criteria: Inclusion Criteria:

1. Informed consent: A signed and dated written informed consent obtained prior to any study-related procedures.
2. Sex and age: Male or female aged ≥18 and ≤75 years.
3. Diagnosis of asthma: A documented history of asthma for at least 1 year, with onset before age 40
4. Stable asthma therapy: Use of medium-dose ICS with or without a LABA or high-dose ICS alone for 3 months (at a stable dose for at least 4 weeks prior to screening).
5. Lung function: Subjects with a pre-bronchodilator FEV1 ≥40% and ≤85% of predicted, after appropriate washout from bronchodilators, at the screening and randomization visits. In addition, the absolute value of the first pre-dose FEV1 at randomization (V2) must be at least 80% of the pre-bronchodilator value attained at screening.
6. Reversibility post-bronchodilator: Subjects with a positive reversibility to bronchodilator at screening, defined as an increase in FEV1 \> 12% and \> 200mL compared to baseline within 30 minutes after 4 inhalations of albuterol HFA pMDI 90µg/actuation.

   Note for IC#5 and IC#6: In case the reversibility and/or quality threshold is not met at screening, the test can be performed once before randomization.
7. Female subjects:

   a. 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 signing of the informed consent form and until the follow-up contact or ii. WOCBP with non-fertile male partners (contraception is not required in this case).

   b. Female subjects of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile as per definitions given in Appendix 2). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges).
8. Cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary/peak flow meter.

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, COPD (as defined by the current 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, 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-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.

Primary outcomes:
measure: Change from baseline in FEV1 Area Under the Curve from 0 to 12 hours post-dose (AUC0-12h) at Week 12 calculated as the difference of the values for CHF 1535 pMDI 800/24µg total daily dose (TDD) and CHF 718 pMDI 800µg TDD.
timeFrame: Week 12
Secondary outcomes:
measure: Change from baseline in peak FEV1 within the first 3 hours post-dose at Week 12 calculated as the difference of the values for CHF 1535 pMDI 800/24µg TDD and CHF 718 pMDI 800µg TDD.
timeFrame: Week 12
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Chiesi Clinical Trial Site 840858
state: Alabama
city: Chandler
country: United States
facility: Chiesi Clinical Trial Site 840895
state: Arizona
city: Encinitas
country: United States
facility: Chiesi Clinical Trial Site 840856
state: California
city: Huntington Beach
country: United States
facility: Chiesi Clinical Trial Site 840843
state: California
city: Huntington Beach
country: United States
facility: Chiesi Clinical Trial Site 840860
state: California
city: Long Beach
country: United States
facility: Chiesi Clinical Trial Site 840896
state: California
city: Los Angeles
country: United States
facility: Chiesi Clinical Trial Site 840883
state: California
city: Los Angeles
country: United States
facility: Chiesi Clinical Trial Site 840810
state: California
city: Newport Beach
country: United States
facility: Chiesi Clinical Trial Site 840869
state: California
city: North Hollywood
country: United States
facility: Chiesi Clinical Trial Site 840890
state: California
city: Northridge
country: United States
facility: Chiesi Clinical Trial Site 840808
state: California
city: Pomona
country: United States
facility: Chiesi Clinical Trial Site 840879
state: California
city: Sacramento
country: United States
facility: Chiesi Clinical Trial Site 840868
state: California
city: San Diego
country: United States
facility: Chiesi Clinical Trial Site 840849
state: California
city: San Diego
country: United States
facility: Chiesi Clinical Trial Site 840877
state: California
city: San Jose
country: United States
facility: Chiesi Clinical Trial Site 840861
state: California
city: Westminster
country: United States
facility: Chiesi Clinical Trial Site 840881
state: California
city: Colorado Springs
country: United States
facility: Chiesi Clinical Trial Site 840873
state: Colorado
city: Denver
country: United States
facility: Chiesi Clinical Trial Site 840800
state: Colorado
city: Coral Gables
country: United States
facility: Chiesi Clinical Trial Site 840820
state: Florida
city: Cutler Bay
country: United States
facility: Chiesi Clinical Trial Site 840841
state: Florida
city: Greenacres City
country: United States
facility: Chiesi Clinical Trial Site 840817
state: Florida
city: Hialeah
country: United States
facility: Chiesi Clinical Trial Site 840822
state: Florida
city: Hialeah
country: United States
facility: Chiesi Clinical Trial Site 840838
state: Florida
city: Kissimmee
country: United States
facility: Chiesi Clinical Trial Site 840864
state: Florida
city: Miami Gardens
country: United States
facility: Chiesi Clinical Trial Site 840809
state: Florida
city: Miami Lakes
country: United States
facility: Chiesi Clinical Trial Site 840863
state: Florida
city: Miami Lakes
country: United States
facility: Chiesi Clinical Trial Site 840865
state: Florida
city: Miami Springs
country: United States
facility: Chiesi Clinical Trial Site 840831
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840814
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840819
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840875
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840887
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840821
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840829
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840828
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840847
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840818
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840802
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840835
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840806
state: Florida
city: Miami
country: United States
facility: Chiesi Clinical Trial Site 840855
state: Florida
city: Palmetto Bay
country: United States
facility: Chiesi Clinical Trial Site 840839
state: Florida
city: Pembroke Pines
country: United States
facility: Chiesi Clinical Trial Site 840840
state: Florida
city: Pembroke Pines
country: United States
facility: Chiesi Clinical Trial Site 840827
state: Florida
city: Port Saint Lucie
country: United States
facility: Chiesi Clinical Trial Site 840811
state: Florida
city: Saint Petersburg
country: United States
facility: Chiesi Clinical Trial Site 840889
state: Florida
city: Saint Petersburg
country: United States
facility: Chiesi Clinical Trial Site 840834
state: Florida
city: Saint Petersburg
country: United States
facility: Chiesi Clinical Trial Site 840880
state: Florida
city: Tallahassee
country: United States
facility: Chiesi Clinical Trial Site 840807
state: Florida
city: Adairsville
country: United States
facility: Chiesi Clinical Trial Site 840871
state: Georgia
city: White Marsh
country: United States
facility: Chiesi Clinical Trial Site 840824
state: Maryland
city: North Dartmouth
country: United States
facility: Chiesi Clinical Trial Site 840826
state: Massachusetts
city: Columbia
country: United States
facility: Chiesi Clinical Trial Site 840859
state: Missouri
city: Saint Charles
country: United States
facility: Chiesi Clinical Trial Site 840888
state: Missouri
city: Saint Louis
country: United States
facility: Chiesi Clinical Trial Site 840846
state: Missouri
city: Bellevue
country: United States
facility: Chiesi Clinical Trial Site 840867
state: Nebraska
city: Henderson
country: United States
facility: Chiesi Clinical Trial Site 840897
state: Nevada
city: North Las Vegas
country: United States
facility: Chiesi Clinical Trial Site 840872
state: Nevada
city: Brick
country: United States
facility: Chiesi Clinical Trial Site 840836
state: New Jersey
city: Albuquerque
country: United States
facility: Chiesi Clinical Trial Site 840851
state: New Mexico
city: Monroe
country: United States
facility: Chiesi Clinical Trial Site 840899
state: North Carolina
city: Raleigh
country: United States
facility: Chiesi Clinical Trial Site 840852
state: North Carolina
city: Edmond
country: United States
facility: Chiesi Clinical Trial Site 840866
state: Oklahoma
city: Tulsa
country: United States
facility: Chiesi Clinical Trial Site 840878
state: Oklahoma
city: Grants Pass
country: United States
facility: Chiesi Clinical Trial Site 840884
state: Oregon
city: Medford
country: United States
facility: Chiesi Clinical Trial Site 840830
state: Oregon
city: Portland
country: United States
facility: Chiesi Clinical Trial Site 840853
state: Oregon
city: Warwick
country: United States
facility: Chiesi Clinical Trial Site 840885
state: Rhode Island
city: Anderson
country: United States
facility: Chiesi Clinical Trial Site 840892
state: South Carolina
city: Columbia
country: United States
facility: Chiesi Clinical Trial Site 840844
state: South Carolina
city: Greenville
country: United States
facility: Chiesi Clinical Trial Site 840850
state: South Carolina
city: Rock Hill
country: United States
facility: Chiesi Clinical Trial Site 840894
state: South Carolina
city: Spartanburg
country: United States
facility: Chiesi Clinical Trial Site 840891
state: South Carolina
city: Knoxville
country: United States
facility: Chiesi Clinical Trial Site 840812
state: Tennessee
city: Baytown
country: United States
facility: Chiesi Clinical Trial Site 840815
state: Texas
city: Boerne
country: United States
facility: Chiesi Clinical Trial Site 840874
state: Texas
city: Carrollton
country: United States
facility: Chiesi Clinical Trial Site 840845
state: Texas
city: Dallas
country: United States
facility: Chiesi Clinical Trial Site 840876
state: Texas
city: El Paso
country: United States
facility: Chiesi Clinical Trial Site 840803
state: Texas
city: Houston
country: United States
facility: Chiesi Clinical Trial Site 840833
state: Texas
city: McKinney
country: United States
facility: Chiesi Clinical Trial Site 840862
state: Texas
city: McKinney
country: United States
facility: Chiesi Clinical Trial Site 840816
state: Texas
city: San Antonio
country: United States
facility: Chiesi Clinical Trial Site 840842
state: Texas
city: San Antonio
country: United States
facility: Chiesi Clinical Trial Site 840857
state: Texas
city: San Antonio
country: United States
facility: Chiesi Clinical Trial Site 840823
state: Texas
city: Sugar Land
country: United States
facility: Chiesi Clinical Trial Site 840801
state: Texas
city: Murray
country: United States
facility: Chiesi Clinical Trial Site 840893
state: Utah
city: Riverton
country: United States
facility: Chiesi Clinical Trial Site 840837
state: Utah
city: Bellingham
country: United States
facility: Chiesi Clinical Trial Site 840882
state: Washington
city: Greenfield
country: United States
facility: Chiesi Clinical Trial Site 840870
state: Wisconsin
Study officials:
affiliation: Allergy and Asthma Specialists Medical Group and Research Center
name: Steven F. Weinstein, M.D.
role: PRINCIPAL_INVESTIGATOR
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