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

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 withdiagnosis before the age of 50 years

4. Stable asthma therapy: a stable maintenance treatment with medium to high dose ofinhaled corticosteroids plus long acting β2 agonists for at least 3 months prior toscreening

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 tohospitalisation or 2 or more asthma exacerbations within the last 12 months

9. A cooperative attitude and ability to use inhalers and to comply with studyprocedures

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 intensivecare unit

3. Recent exacerbation or respiratory tract infection within 4 weeks prior to screeningvisit or during the run-in period

4. Subjects using systemic corticosteroids medication in the 4 weeks or slow-releasecorticosteroids in the 12 weeks prior to randomisation

5. Asthma requiring use of biologics

6. Respiratory disorders other than asthma: subjects with known respiratory disordersother 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 useof 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 intercurrentillness, or any clinically relevant abnormal findings in haematology, clinicalchemistry, or urinalysis

13. Subjects with a diagnosis of depression, generalised anxiety disorder, suicidalideation or behaviour

14. Patients mentally or legally incapacitated or patients accommodated in anestablishment

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 plannedduring the trial

20. Subjects treated with non-potassium sparing diuretics, nonselective β-blockingdrugs, quinidine, quinidine like anti-arrhythmic, or any medication with a QTcprolongation potential or a history of QTc prolongation

21. Subjects treated with monoamine oxidase inhibitors (MAOIs) and tricyclicanti-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 duringthe run-in period.

26. For females only: pregnant or lactating women