An 8-week Dose Ranging Study of CHF 718 pMDI in Asthmatic Subjects

An 8-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 3 Doses of CHF 718 pMDI (HFA Beclomethasone Dipropionate Via Pressured Metered Dose Inhaler) in Asthmatic Subjects.

The purpose of this study is to evaluate the dose-response of different doses of CHF 781 Pressurized Metered Dose Inhaler (pMDI) on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target patient population.

This is a phase II, multicenter, randomized, double-blind, placebo and active controlled dose ranging 5-arm parallel group study to identify the optimal dose of CHF 781 pMDI with respect to lung function and other clinical efficacy and safety outcomes.

After a 2 week run-in period under rescue albuterol as needed and background inhaled corticosteroid (ICS), patients will be randomized to one of the 5 study treatment groups. After randomization, patients will be assessed after 4 and 8 weeks of study treatment at the center. A follow-up phone call will be performed a week after the last visit.

During the study, daily asthma symptoms, peak expiratory flow, rescue and background medication use, and compliance with the study medication will be recorded via subject diary. Treatment-Emergent Adverse Events (TEAEs) will be assessed and recorded throughout the study. At screening and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurements, and 12-lead ECG. Routine hematology, blood chemistry, and pregnancy testing will be performed before enrollment and at end of study. 24-hr urine cortisol and creatinine will be assessed before and after the first dose and just before the last dose of study treatment.

Inclusion Criteria:

• Male or female subjects aged ≥18 and ≤75 years who have signed an Informed Consent form prior to initiation of any study-related procedure.
• A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report, 2016, documented for at least 1 year prior to screening.
• Subjects with poorly controlled or uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire 7 © (ACQ-7) ≥1.5 (this criterion must be met at screening and at randomization visits).
• Subjects with a pre-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) ≥50% and <85% of their predicted normal value, after appropriate washout from bronchodilators, at the screening and randomization visits.
• Subjects with a positive response to a reversibility test at screening (pre - post BD), within 1 year prior to or at screening defined as ΔFEV1≥12% and ≥200 mL over baseline within 30 minutes after inhaling 4 puffs of albuterol HFA 90µg/actuation.
• Use of inhaled corticosteroids (low/medium dose according to GINA Report 2016) with or without a long-acting bronchodilator (LABD) for 3 months (stable dose in the last 4 weeks) before screening visit (V).
• A cooperative attitude and ability to demonstrate correct use of the diary, peak flow meter, and pMDI inhalers.
• A basal morning (7-10 am) serum cortisol level between 7-28 µg/dL at screening visit (V1).
• A Body Mass Index (BMI): 18.5 ≤ BMI <35 kg/m^2.

Exclusion Criteria:

• Pregnant (as evident by a positive urine human chorionic gonadotropin (hCG) or serum β-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use a highly effective birth control method
• Subjects who suffer from chronic obstructive pulmonary disease (COPD) as defined by the GOLD Report 2017, or are suspected of having Asthma COPD Overlap Syndrome (ACOS) as defined in GINA Report, 2016.
• Inability to carry out pulmonary lung function testing, to comply with study procedures or with study drug intake.
• Current smokers or ex-smokers (tobacco, vapor cigarettes, marijuana) with a smoking history of >10 pack-years or having stopped smoking one year or less prior to screening visit.
• History of life-threatening asthma, clinically significant uncontrolled disease or respiratory infection.
• An asthma exacerbation requiring oral corticosteroids within 3 months or hospitalization within 6 months prior to screening.
• Subjects with unresolved bacterial or viral respiratory tract, sinus or middle ear infection affecting asthma status within 2 weeks prior to screening.
• Subjects who received a vaccination within 2 weeks prior to screening or during the run-in.
• Subjects with oral candidiasis at screening or at randomization.
• Subjects with any clinically significant, uncontrolled condition
• Subjects who have clinically significant cardiovascular condition
• Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement.
• Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) >450 ms for males or QTcF >470 ms for females at screening and randomization visits.
• Subjects with known intolerance/hypersensitivity or contra-indication to treatment with ß2-adrenergic receptor agonists, inhaled corticosteroids or propellant gases/excipients.
• Subjects with concomitant immunosuppressive therapy, use of oral or injected corticosteroids, anti-Immunoglobulin E (IgE), anti-Interleukin 5 (IL5), or other monoclonal or polyclonal antibodies within 12 weeks prior to screening.
• Use of potent cytochrome P450 3A4 inhibitors and inducers within 4 weeks prior to screening.
• History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening.
• 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.
• Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order.
• Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.