Uncontrolled Asthma
Conditions
Keywords
Asthma, PDE4 inhibitor, anti-inflammatory respiratory drug, Tanimilast
Brief summary
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)
Interventions
DRUGExperimental: CHF6001 3200 μg
800 μg/actuation - 2 inhalations of CHF6001 800 μg twice daily (BID) total daily dose 3200 μg
DRUGPlacebo Comparator: CHF6001 Placebo
2 inhalations of CHF6001 matching placebo BID
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double (Participant, Investigator)
Intervention model description
Randomised, double-blind, placebo-controlled, 2-arm parallel group study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Asthma exacerbation over 52 weeks of treatment | Over 52 weeks | Number of Asthma exacerbation over 52 weeks of treatment (Asthma exacerbations defined as severe event with worsening of asthma requiring at least 3 days of SCS use with or without emergency visit or hospitalization) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of asthma exacerbation and asthma worsening over 52 weeks of treatment | Up to 52 weeks | Asthma exacerbations defined as severe event with worsening of asthma requiring at least 3 days of SCS use with or without emergency visit or hospitalization; Asthma worsening defined as moderate asthma exacerbation. |
| Time to first asthma exacerbation or asthma worsening | Up to 52 weeks | Asthma exacerbations defined as severe event with worsening of asthma requiring at least 3 days of SCS use with or without emergency visit or hospitalization; Asthma worsening defined as moderate asthma exacerbation. |
| ACQ-7 responders | week 4, week 26 and week 52 | ACQ-7 responders at Week 4, Week 26 and Week 52 (i.e., subjects showing improvement from baseline in ACQ-7 score of ≥0.5 units); |
| Change from baseline in ACQ-7 and ACQ-6 | week 4, week 26 and week 52 | Change from baseline in ACQ-7 and ACQ-6 at Week 4, Week 26 and Week 52 |
| Change from baseline in Mini-AQLQ | week 4, week 26 and week 52 | Change from baseline in Mini-AQLQ at Week 4, Week 26 and Week 52 |
| Time to first asthma exacerbation; | Up to 52 weeks | Asthma exacerbations defined as severe event with worsening of asthma requiring at least 3 days of SCS use with or without emergency visit or hospitalization |
| Change from baseline in pre-dose FVC | Week4, Week 52 and Week 26 | Change from baseline in pre-dose FVC at Week4, Week 52 and Week 26; |
| Change from baseline (run-in period) to each inter-visit period and to the entire treatment period in pre dose morning/evening PEF; | Up to 52 weeks | — |
| Change from baseline to each inter-visit period and to the entire treatment period in the average rescue medication use (number of puffs/day) and asthma symptoms score | Up to 52 weeks | — |
| Change from baseline to each inter-visit period and to the entire treatment period in the percentage of rescue medication-free days, asthma symptoms-free days and asthma control days. | Up to 52 weeks | — |
| Change from baseline in pre-dose FEV1 | week 4, week 26 and week 52 | Change from baseline in pre-dose FEV1 at Week 4, Week 26 and Week 52; |
Countries
Argentina, Bulgaria, Czechia, Georgia, Germany, Hungary, Italy, Latvia, Lithuania, Poland, Romania, South Africa, South Korea, Spain
Outcome results
None listed