A 52-week, Placebo- and Active- Controlled (Roflumilast, Daliresp® 500µg) Study to Evaluate the Efficacy and Safety of Two Doses of CHF6001 DPI (Tanimilast) as add-on to Maintenance Triple Therapy in Subjects With COPD and Chronic Bronchitis. (PILLAR)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and the safety of two doses of CHF6001 (Tanimilast) as add-on to maintenance triple therapy in the target patient population.

Official Title
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A 52-week, Randomized, Double-blind, Double-dummy, Placebo- and Active- Controlled (Roflumilast, Daliresp® 500µg), Parallel Group, Study to Evaluate the Efficacy and Safety of Two Doses of CHF6001 DPI add-on to Maintenance Triple Therapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis.

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: CHF6001 1600µg
* Drug: CHF6001 3200µg
* Drug: Placebo
* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥ 40 years, with COPD and with chronic bronchitis. Current smokers or ex-smokers (history of ≥10 pack years). Post-bronchodilator FEV1 <50% of the patient predicted normal value and FEV1/FVC ratio < 0.7. At least, one moderate or severe COPD exacerbation in the previous year. CAT score ≥10. Subjects on regular maintenance triple therapy for at least 12 months. Exclusion Criteria: Subjects with current asthma. Subjects with moderate or severe COPD exacerbation 4 weeks before study entry and randomisation Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD. Subjects with primary diagnosis of emphysema not related to COPD. Subjects with known respiratory disorders other than COPD. Subjects with lung volume reduction surgery. Subjects with active cancer or a history of lung cancer. Subjects under Roflumilast treatment within 6 months before study entry. Subjects with a diagnosis of depression, generalised anxiety disorder, suicidal ideation. Subjects with clinically significant cardiovascular condition. Subjects with neurological disease. Subjects with clinically significant laboratory abnormalities. Subjects with moderate or severe hepatic impairment.

Ages Eligible for Study
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Minimum Age: 40 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF6001 1600µg<br> | Drug: CHF6001 1600µg<br>* CHF6001 400µg, 2 inhalations bid (total daily dose of 1600µg) and Roflumilast matching placebo, 1 tablet once daily<br>|
| Experimental: CHF6001 3200µg<br> | Drug: CHF6001 3200µg<br>* CHF6001 800µg, 2 inhalations bid (total daily dose of 3200µg) and Roflumilast matching placebo, 1 tablet once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* CHF6001 matching placebo, 2 inhalations bid and Roflumilast matching placebo, 1 tablet once daily<br>|
| Active Comparator: Roflumilast<br> | Drug: Roflumilast<br>* - 1 tablet of Roflumilast (Daliresp®), 250µg, once daily during the first 4 weeks of treatment then 1 tablet of Roflumilast (Daliresp®), 500µg, once daily for the remaining treatment period and CHF6001 matching placebo, 2 inhalations bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of moderate and severe exacerbations occurring during the planned 52-week treatment period. | Moderate or severe exacerbation is defined by symptomatic worsening of COPD: Moderate : requiring use of systemic corticosteroids (oral/IV/IM corticosteroids), and/or use of antibiotics Severe : requiring hospitalisation or resulting in death | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to first moderate or severe exacerbation. |  | Up to 52 weeks | 
| The annual rate of severe exacerbations. |  | Up to 52 weeks | 
| The time to first severe exacerbation. |  | Up to 52 weeks | 
| The number of all on-treatment severe exacerbations. |  | Up to 52 weeks | 
| The number of all on-treatment exacerbations requiring systemic corticosteroids. |  | Up to 52 weeks | 
| Change from baseline (pre-dose Visit 2) in pre-dose FEV1, at week 52. |  | At week 52 | 
| Change from baseline in SGRQ total and domain scores at week 52. |  | At week 52 | 
| SGRQ response (change from baseline SGRQ total score ≤ -4) at week 52. |  | At week 52 | 
| Change from baseline to last inter-visit period (week 40-52) in E-RS Total and subscale scores. |  | Up to 52 weeks | 
| E-RS response (change from baseline E-RS Total score ≤ -2) at week 52. |  | At week 52 | 
| Change from baseline to last inter-visit period (week 40-52) in the percentage of days without intake of rescue medication and in the average rescue medication use (number of puffs). |  | Up to 52 weeks | 
| Time to study medication discontinuation for any reason. |  | Up to 52 weeks | 
| Time to moderate or severe exacerbation or study medication discontinuation due to any adverse event, lack of efficacy or death (composite endpoint) and time to study medication discontinuation component. |  | Up to 52 weeks | 
| Time to first moderate/severe exacerbation or study medication discontinuation due to any class-related AE, lack of efficacy, or death (composite endpoint) and time to study medication discontinuation component. |  | Up to 52 weeks | 
| Key Secondary Variable: Change from baseline in SGRQ Total score at week 52 |  | At week 52 | 

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