An 8-week Dose Ranging Study of CHF 718 pMDI in Asthmatic Subjects
Condition: Asthma
MeSH terms: Asthma
Intervention: CHF 718 pMDI; Placebo pMDI; Beclomethasone Dipropionate (BDP)
Intervention description: Dose Response: Test one of three different doses of CHF 718 pMDI; Placebo Control; Active Control
Intervention MeSH terms: Beclomethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 610.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.