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

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 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 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 ≥200mL 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 LABD for 3 months (stable dose in the last 4 weeks) before screening visit

- 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 (V1).

- A Body Mass Index: 18.5 ≤ BMI <35 kg/m2.

Exclusion Criteria:

- Pregnant (as evident by a positive urine 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 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) >450ms for
males or QTcF >470ms 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-IgE, anti-IL5 or other monoclonal or polycolonal 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.