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
- Conditions
- Asthma
- Interventions
- Drug: Beclomethasone Dipropionate/Formoterol Fumarate
- Registration Number
- NCT05292586
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1377
-
Informed consent: A signed and dated written informed consent obtained prior to any study-related procedures.
-
Sex and age: Male or female aged ≥18 and ≤75 years.
-
Diagnosis of asthma: A documented history of asthma for at least 1 year, with onset before age 40
-
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).
-
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.
-
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.
-
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).
-
Cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary/peak flow meter.
- 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).
- Poor compliance with run-in medication or eDiary completion <50% before randomization.
- 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.
- 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.
- 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.
- Unstable ICS dose during the 4 weeks prior to screening visit, including any change in dose, schedule, or formulation.
- Use of systemic corticosteroid medication in the 4 weeks prior to screening or slow-release corticosteroids in the 12 weeks before screening.
- 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.
- 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.
- E-cigarette status: Current e-cigarettes users at the time of the screening visit.
- Cannabis usage: Current use of inhaled or oral cannabis products (e.g. marijuana).
- Substance abuse: Subjects with a history of alcohol or substance/drug abuse within 12 months prior to screening.
- 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.
- 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).
- 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.
- Vaccination: Subjects having received a vaccination within 2 weeks prior to screening or during the run-in period.
- Subjects' wellbeing: Subjects mentally or legally incapacitated, including but not limited to subjects who are institutionalized or incarcerated.
- Hypersensitivity: Subjects with known intolerance, hypersensitivity or contraindication to treatment with ß2-agonists, ICS, or propellant gases/excipients.
- Surgery: Subjects with major surgery in the 3 months prior to the screening visit or planned surgery during the study.
- 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.
- Subjects treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants.
- 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.
- Subjects who are receiving any therapy that could interfere with the study drugs according to investigator's opinion.
- 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.
- 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 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. Week 12
- Secondary Outcome Measures
Name Time Method 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. Week 12
Trial Locations
- Locations (91)
Chiesi Clinical Trial Site 840833
🇺🇸Houston, Texas, United States
Chiesi Clinical Trial Site 840819
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840887
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840875
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840828
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840818
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840802
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840847
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840806
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840893
🇺🇸Murray, Utah, United States
Chiesi Clinical Trial Site 840882
🇺🇸Bellingham, Washington, United States
Chiesi Clinical Trial Site 840837
🇺🇸Riverton, Utah, United States
Chiesi Clinical Trial Site 840870
🇺🇸Greenfield, Wisconsin, United States
Chiesi Clinical Trial Site 840842
🇺🇸San Antonio, Texas, United States
Chiesi Clinical Trial Site 840857
🇺🇸San Antonio, Texas, United States
Chiesi Clinical Trial Site 840823
🇺🇸San Antonio, Texas, United States
Chiesi Clinical Trial Site 840872
🇺🇸North Las Vegas, Nevada, United States
Chiesi Clinical Trial Site 840891
🇺🇸Spartanburg, South Carolina, United States
Chiesi Clinical Trial Site 840850
🇺🇸Greenville, South Carolina, United States
Chiesi Clinical Trial Site 840892
🇺🇸Anderson, South Carolina, United States
Chiesi Clinical Trial Site 840844
🇺🇸Columbia, South Carolina, United States
Chiesi Clinical Trial Site 840836
🇺🇸Brick, New Jersey, United States
Chiesi Clinical Trial Site 840853
🇺🇸Portland, Oregon, United States
Chiesi Clinical Trial Site 840895
🇺🇸Chandler, Arizona, United States
Chiesi Clinical Trial Site 840814
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840821
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840835
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840812
🇺🇸Knoxville, Tennessee, United States
Chiesi Clinical Trial Site 840868
🇺🇸Sacramento, California, United States
Chiesi Clinical Trial Site 840858
🇺🇸Mobile, Alabama, 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 840856
🇺🇸Encinitas, California, United States
Chiesi Clinical Trial Site 840883
🇺🇸Los Angeles, California, United States
Chiesi Clinical Trial Site 840896
🇺🇸Long Beach, California, United States
Chiesi Clinical Trial Site 840810
🇺🇸Los Angeles, California, United States
Chiesi Clinical Trial Site 840890
🇺🇸North Hollywood, California, United States
Chiesi Clinical Trial Site 840869
🇺🇸Newport Beach, California, United States
Chiesi Clinical Trial Site 840808
🇺🇸Northridge, California, United States
Chiesi Clinical Trial Site 840879
🇺🇸Pomona, California, United States
Chiesi Clinical Trial Site 840849
🇺🇸San Diego, California, United States
Chiesi Clinical Trial Site 840877
🇺🇸San Diego, California, United States
Chiesi Clinical Trial Site 840861
🇺🇸San Jose, California, United States
Chiesi Clinical Trial Site 840881
🇺🇸Westminster, California, United States
Chiesi Clinical Trial Site 840873
🇺🇸Colorado Springs, Colorado, United States
Chiesi Clinical Trial Site 840800
🇺🇸Denver, Colorado, United States
Chiesi Clinical Trial Site 840820
🇺🇸Coral Gables, Florida, United States
Chiesi Clinical Trial Site 840841
🇺🇸Cutler Bay, Florida, United States
Chiesi Clinical Trial Site 840817
🇺🇸Greenacres City, Florida, United States
Chiesi Clinical Trial Site 840822
🇺🇸Hialeah, Florida, United States
Chiesi Clinical Trial Site 840838
🇺🇸Hialeah, Florida, United States
Chiesi Clinical Trial Site 840864
🇺🇸Kissimmee, Florida, United States
Chiesi Clinical Trial Site 840865
🇺🇸Miami Lakes, Florida, United States
Chiesi Clinical Trial Site 840809
🇺🇸Miami Gardens, Florida, United States
Chiesi Clinical Trial Site 840863
🇺🇸Miami Lakes, Florida, United States
Chiesi Clinical Trial Site 840831
🇺🇸Miami Springs, Florida, United States
Chiesi Clinical Trial Site 840829
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840855
🇺🇸Miami, Florida, United States
Chiesi Clinical Trial Site 840827
🇺🇸Pembroke Pines, Florida, United States
Chiesi Clinical Trial Site 840840
🇺🇸Pembroke Pines, Florida, United States
Chiesi Clinical Trial Site 840839
🇺🇸Palmetto Bay, Florida, United States
Chiesi Clinical Trial Site 840834
🇺🇸Saint Petersburg, Florida, United States
Chiesi Clinical Trial Site 840889
🇺🇸Saint Petersburg, Florida, United States
Chiesi Clinical Trial Site 840880
🇺🇸Saint Petersburg, Florida, United States
Chiesi Clinical Trial Site 840811
🇺🇸Port Saint Lucie, Florida, United States
Chiesi Clinical Trial Site 840871
🇺🇸Adairsville, Georgia, United States
Chiesi Clinical Trial Site 840807
🇺🇸Tallahassee, Florida, United States
Chiesi Clinical Trial Site 840888
🇺🇸Saint Charles, Missouri, United States
Chiesi Clinical Trial Site 840826
🇺🇸North Dartmouth, Massachusetts, United States
Chiesi Clinical Trial Site 840824
🇺🇸White Marsh, Maryland, United States
Chiesi Clinical Trial Site 840859
🇺🇸Columbia, Missouri, United States
Chiesi Clinical Trial Site 840846
🇺🇸Saint Louis, Missouri, United States
Chiesi Clinical Trial Site 840867
🇺🇸Bellevue, Nebraska, United States
Chiesi Clinical Trial Site 840897
🇺🇸Henderson, Nevada, United States
Chiesi Clinical Trial Site 840899
🇺🇸Monroe, North Carolina, United States
Chiesi Clinical Trial Site 840866
🇺🇸Edmond, Oklahoma, United States
Chiesi Clinical Trial Site 840852
🇺🇸Raleigh, North Carolina, United States
Chiesi Clinical Trial Site 840884
🇺🇸Grants Pass, Oregon, United States
Chiesi Clinical Trial Site 840878
🇺🇸Tulsa, Oklahoma, United States
Chiesi Clinical Trial Site 840830
🇺🇸Medford, Oregon, United States
Chiesi Clinical Trial Site 840885
🇺🇸Warwick, Rhode Island, United States
Chiesi Clinical Trial Site 840894
🇺🇸Rock Hill, South Carolina, United States
Chiesi Clinical Trial Site 840815
🇺🇸Baytown, Texas, United States
Chiesi Clinical Trial Site 840803
🇺🇸El Paso, Texas, United States
Chiesi Clinical Trial Site 840874
🇺🇸Boerne, Texas, United States
Chiesi Clinical Trial Site 840845
🇺🇸Carrollton, Texas, United States
Chiesi Clinical Trial Site 840876
🇺🇸Dallas, Texas, United States
Chiesi Clinical Trial Site 840862
🇺🇸McKinney, Texas, United States
Chiesi Clinical Trial Site 840816
🇺🇸McKinney, Texas, United States
Chiesi Clinical Trial Site 840801
🇺🇸Sugar Land, Texas, United States
Chiesi Clinical Trial Site 840851
🇺🇸Albuquerque, New Mexico, United States