A Dose Ranging Study of CHF 1531 in Asthmatic Subjects

This is a phase II, randomized, double-blind, placebo and active controlled dose-ranging, 6
arm incomplete block cross-over study to identify the optimal dose of CHF 1531 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), qualifying subjects will be required to complete 4 treatment periods of
2 weeks each separated by a 2 week wash-out intervals. During each treatment period, the
subject will be randomly assigned to take one of 5 double-blind study treatments twice daily
(one of 4 doses of CHF 1531 or a matching placebo) or the open-label active control treatment
also twice daily. All subjects will concomitantly receive ICS treatment with QVAR® inhaler
(beclomethasone dipropionate 40 or 80 µg /actuation) twice daily at a dose that matches their
pre-enrollment ICS, and an albuterol inhaler to use as needed as asthma rescue medication,
during the entire study. The subjects will visit the study center every 2 weeks to undergo
study procedures, and will receive a safety follow-up phone call one week after their last
visit. In total, the study will last 18 weeks and will require 10 visits to the study center.

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.
A full physical exam, routine hematology, blood chemistry, spirometry, vital signs
measurement, 12-lead ECG and pregnancy testing will be performed before enrollment and at end
of study. Furthermore on Day 1 and 14 of each treatment period, serial spirometry, 12-lead
ECGs, BP, and serum potassium and glucose will also be measured at the study center up to 12
hours post-dosing.

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.

- Poorly controlled or uncontrolled asthma evidenced by a score ≥1.5 on the Asthma
Control Questionnaire 7 © (ACQ-7)

- A pre-bronchodilator FEV1 ≥60% 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, defined as
ΔFEV1 ≥12% and ≥200mL over baseline within 30 minutes after inhaling 4 puffs of
albuterol HFA 90µg/actuation.

- Use of ICS (low/medium dose according to GINA Report, 2016) with or without a LABD for
3 months (at a 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 inhaler.

Exclusion Criteria:

- Pregnant or lactating women and all women physiologically capable of becoming pregnant
UNLESS they are willing to use a highly effective birth control methods

- Subjects who suffer from COPD as defined by the GOLD Report, 2017, or are suspected of
having Asthma COPD Overlap Syndrome (ACOS) as described in the GINA Report, 2016.

- Inability to carry out pulmonary 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/intravenous corticosteroids ≤ 30 days,
intramuscular depot corticosteroid ≤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 and at randomization.

- Subjects with any clinically significant, uncontrolled condition.

- Subjects with serum potassium levels <3.5 mEq/L (or 3.5 mmol/L) at screening.

- 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 patient according to Investigator's
judgment.

- Subjects whose 12-lead ECG shows Fridericia's corrected QT interval (QTcF) >450ms for
males or QTcF >470ms for females at screening or randomization visits.

- Subjects with known intolerance/hypersensitivity or contra-indication to treatment
with inhaled β2-adrenergic receptor agonists, corticosteroids or propellant
gases/excipients.

- 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.

- 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.