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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Uncontrolled Asthma

Intervention / Treatment
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* Drug: Experimental: CHF6001 3200 μg
* Drug: Placebo Comparator: CHF6001 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's written informed consent Male or female subjects aged ≥18 and ≤75 years A documented history of physician-diagnosed asthma for at least 1 year and with diagnosis before the age of 50 years 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 A prebronchodilator FEV1 ≤80% of the predicted normal value Bronchodilator responsiveness after inhalation of salbutamol or equivalent Evidence of poorly controlled or uncontrolled asthma as based on an ACQ-7 score ≥1.5 History of asthma exacerbations : at least 1 asthma exacerbation leading to hospitalisation or 2 or more asthma exacerbations within the last 12 months A cooperative attitude and ability to use inhalers and to comply with study procedures Exclusion Criteria: e-Diary completion compliance <75% during run-in History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit Recent exacerbation or respiratory tract infection within 4 weeks prior to screening visit or during the run-in period Subjects using systemic corticosteroids medication in the 4 weeks or slow-release corticosteroids in the 12 weeks prior to randomisation Asthma requiring use of biologics Respiratory disorders other than asthma: subjects with known respiratory disorders other than asthma Subjects with a history of lung volume resection Current smokers, ex-smokers with a smoking history of ≥10 pack-years or current use of inhaled or oral cannabis products. Subjects with cancer or history of cancer Subjects with cardiovascular diseases Subjects with any abnormal and clinically significant 12-lead ECG Subjects with previous medical history, evidence of an uncontrolled intercurrent illness, or any clinically relevant abnormal findings in haematology, clinical chemistry, or urinalysis Subjects with a diagnosis of depression, generalised anxiety disorder, suicidal ideation or behaviour Patients mentally or legally incapacitated or patients accommodated in an establishment Subjects with liver diseases Drugs with hepatoxicity potential Subjects with contra-indications to IMPs: Subjects with history alcohol/drug abuse Subjects with major surgery in the 3 months prior to screening visit or planned during the trial 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 Subjects treated with monoamine oxidase inhibitors (MAOIs) and tricyclic anti-depressants Subjects receiving any therapy that could interfere with the study drugs Participation in another investigational trial Documented coronavirus disease 2019 (COVID-19) diagnosis within the last 2 weeks Subjects having received a vaccination within 2 weeks prior to screening or during the run-in period. For females only: pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, double-blind, placebo-controlled, 2-arm parallel group study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF6001 - CHF6001 total daily dose 3200 μg;<br> | Drug: Experimental: CHF6001 3200 μg<br>* 800 μg/actuation - 2 inhalations of CHF6001 800 μg twice daily (BID) total daily dose 3200 μg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo Comparator: CHF6001 Placebo<br>* 2 inhalations of CHF6001 matching placebo BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Asthma exacerbation over 52 weeks of treatment | 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) | Over 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first asthma exacerbation; | 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 | Up to 52 weeks | 
| Number of asthma exacerbation and asthma worsening 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; Asthma worsening defined as moderate asthma exacerbation. | Up to 52 weeks | 
| Time to first asthma exacerbation or asthma worsening | 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. | Up to 52 weeks | 
| ACQ-7 responders | 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); | week 4, week 26 and week 52 | 
| Change from baseline in ACQ-7 and ACQ-6 | Change from baseline in ACQ-7 and ACQ-6 at Week 4, Week 26 and Week 52 | week 4, week 26 and week 52 | 
| Change from baseline in Mini-AQLQ | Change from baseline in Mini-AQLQ at Week 4, Week 26 and Week 52 | week 4, week 26 and week 52 | 
| Change from baseline in pre-dose FEV1 | Change from baseline in pre-dose FEV1 at Week 4, Week 26 and Week 52; | week 4, week 26 and week 52 | 
| Change from baseline in pre-dose FVC | Change from baseline in pre-dose FVC at Week4, Week 52 and Week 26; | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, PDE4 inhibitor, anti-inflammatory respiratory drug, Tanimilast