Efficacy and Safety of Tanimilast in Asthmatics uNcontrolled on ICS-containinG backgrOund Maintenance Therapy

A 52-week, Randomised, Double Blind, Multicentre, 2-arm Parallel Group Trial Assessing Efficacy of CHF6001 (Total Daily Dose 3200μg) Dry Powder Inhaler (DPI) add-on to Maintenance Medium or High Dose of Inhaled Corticosteroids in Combination With Long-acting ß2-agonists in Subjects With Uncontrolled Asthma

The purpose of this study is to evaluate the efficacy and safety of CHF6001 (Tanimilast) as add-on to maintenance of inhaled corticosteroids in combination with Long-acting ß2-agonists in the target patient population. (TANGO)

Inclusion Criteria:

1. Subject's written informed consent
2. Male or female subjects aged ≥18 and ≤75 years
3. A documented history of physician-diagnosed asthma for at least 1 year and with diagnosis before the age of 50 years
4. Stable asthma therapy: a stable maintenance treatment with medium to high dose of inhaled corticosteroids plus long acting β2 agonists for at least 3 months prior to screening
5. A prebronchodilator FEV1 ≤80% of the predicted normal value
6. Bronchodilator responsiveness after inhalation of salbutamol or equivalent
7. Evidence of poorly controlled or uncontrolled asthma as based on an ACQ-7 score ≥1.5
8. History of asthma exacerbations : at least 1 asthma exacerbation leading to hospitalisation or 2 or more asthma exacerbations within the last 12 months
9. A cooperative attitude and ability to use inhalers and to comply with study procedures

Exclusion Criteria:

1. e-Diary completion compliance <75% during run-in
2. History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit
3. Recent exacerbation or respiratory tract infection within 4 weeks prior to screening visit or during the run-in period
4. Subjects using systemic corticosteroids medication in the 4 weeks or slow-release corticosteroids in the 12 weeks prior to randomisation
5. Asthma requiring use of biologics
6. Respiratory disorders other than asthma: subjects with known respiratory disorders other than asthma
7. Subjects with a history of lung volume resection
8. Current smokers, ex-smokers with a smoking history of ≥10 pack-years or current use of inhaled or oral cannabis products.
9. Subjects with cancer or history of cancer
10. Subjects with cardiovascular diseases
11. Subjects with any abnormal and clinically significant 12-lead ECG
12. Subjects with previous medical history, evidence of an uncontrolled intercurrent illness, or any clinically relevant abnormal findings in haematology, clinical chemistry, or urinalysis
13. Subjects with a diagnosis of depression, generalised anxiety disorder, suicidal ideation or behaviour
14. Patients mentally or legally incapacitated or patients accommodated in an establishment
15. Subjects with liver diseases
16. Drugs with hepatoxicity potential
17. Subjects with contra-indications to IMPs:
18. Subjects with history alcohol/drug abuse
19. Subjects with major surgery in the 3 months prior to screening visit or planned during the trial
20. Subjects treated with non-potassium sparing diuretics, nonselective β-blocking drugs, quinidine, quinidine like anti-arrhythmic, or any medication with a QTc prolongation potential or a history of QTc prolongation
21. Subjects treated with monoamine oxidase inhibitors (MAOIs) and tricyclic anti-depressants
22. Subjects receiving any therapy that could interfere with the study drugs
23. Participation in another investigational trial
24. Documented coronavirus disease 2019 (COVID-19) diagnosis within the last 2 weeks
25. Subjects having received a vaccination within 2 weeks prior to screening or during the run-in period.
26. For females only: pregnant or lactating women