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)

Sponsor

Chiesi Farmaceutici S.p.A. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04636814

Collaborator

(none)

3,980

Enrollment

Location

Arms

37.7

Anticipated Duration (Months)

105.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: CHF6001 1600µg Drug: CHF6001 3200µg Drug: Placebo Drug: Roflumilast	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3980 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jul 12, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CHF6001 1600µg	Drug: CHF6001 1600µg CHF6001 400µg, 2 inhalations bid (total daily dose of 1600µg) and Roflumilast matching placebo, 1 tablet once daily
Experimental: CHF6001 3200µg	Drug: CHF6001 3200µg CHF6001 800µg, 2 inhalations bid (total daily dose of 3200µg) and Roflumilast matching placebo, 1 tablet once daily
Placebo Comparator: Placebo	Drug: Placebo CHF6001 matching placebo, 2 inhalations bid and Roflumilast matching placebo, 1 tablet once daily
Active Comparator: Roflumilast	Drug: Roflumilast - 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

Outcome Measures

Primary Outcome Measures

The number of moderate and severe exacerbations occurring during the planned 52-week treatment period. [Up to 52 weeks]
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

Secondary Outcome Measures

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 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 COPD emphysema or mixed phenotypes.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 100524 - Medical Centre New Rehabilitation Centre EOOD	Stara Zagora		Bulgaria

Sponsors and Collaborators

Chiesi Farmaceutici S.p.A.

Investigators

Principal Investigator: Fernando J. MARTINEZ, Prof., Weill Cornell Medical College, New York Presbyterian Hospital, 1305 York avenue box 96 New York 10021 USA