A 52-week, Placebo-controlled Study to Evaluate the Efficacy and Safety of 2 Doses of CHF6001 DPI (Tanimilast), as add-on to Maintenance Triple Therapy in Subjects With COPD and Chronic Bronchitis (PILASTER)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and 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, Placebo-controlled, 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: Experimental: CHF6001 1600µg
* Drug: Experimental: CHF6001 3200µg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥ 40 years with COPD and chronic bronchitis Current or ex-smokers (history ≥ 10 pack years). Post-bronchodilator FEV1 <60% of the subject predicted normal value and FEV1/FVC ratio < 0.7. At least, one moderate or severe COPD exacerbation in previous year. CAT score ≥ 10 Subjects on regular maintenance triple therapy for at least 12 months prior to screening and receiving regular maintenance triple therapy for at least 3 months prior to screening visit Exclusion Criteria: Subjects with current asthma. Subjects with moderate or severe COPD exacerbation 4 weeks prior to study entry and randomization. Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD. Subjects with COPD emphysema or mixed phenotypes. Subjects with known respiratory disorders other than COPD. Subjects with active cancer or a history of lung cancer with full recovery less than 1 year after completing cancer therapy. 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. Subjects with a significant 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: Experimental: CHF6001 1600µg<br>* CHF6001 400µg, 2 inhalations bid (total daily dose of 1600µg).<br>|
| Experimental: CHF6001 3200µg<br> | Drug: Experimental: CHF6001 3200µg<br>* CHF6001 800µg, 2 inhalations bid (total daily dose of 3200µg).<br>|
| Placebo Comparator: CHF6001 Placebo<br> | Drug: Placebo<br>* 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 COPD 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 corticosteroid (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 exacerbation. |  | Up to 52 weeks | 
| The time to first severe exacerbation. |  | Up to 52 weeks | 
| The number of on-treatment severe exacerbations. |  | 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 | 

 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