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A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD (PIONEER)

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

CHF6001

Budesonide

Placebo

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring anti-inflammatory respiratory drug, PDE4 inhibitor

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

COPD patients
Non- childbearing potential or woman permanently sterilized or on one or more highly effective contraception
Current/ex smokers (history > 10 pack years)
Post bronchodilatator FEV1 >=30% and <=70% predicted normal value and FEV1/FVC ratio <0.7
Documented history of at least 1 moderate or severe exacerbation in the 12 months prior to study entry
Symptomatic patients (MMRC score ≥2 and a CAT score ≥10)
Patients on daily maintenance therapy with an ICS/LABA .

Exclusion Criteria:

Diagnosis of asthma or other respiratory disorders
Maintenance bronchodilators therapy only (eg LABA alone)
Maintenance triple therapy.
Occurrence of a moderate or severe COPD exacerbation within 6 weeks prior to study entry or during the run-in period.
Patients requiring long term oxygen therapy.
Concomitant or recent pulmonary rehabilitation programme
Known respiratory disorders other than COPD
Lung cancer or a history of lung cancer, active or history of cancer with less than 5 years disease free survival time
Hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the excipients
Depression, generalised anxiety disorder, suicidal ideation
Any clinically significant cardiovascular disease (IM, CHF III/IV; AF not controlled by therapy, etc) within 1 year of study entry
Any relevant clinically significant cardiovascular condition, clinically abnormal significant 12-lead ECG (QTcF>450 ms for male and >470 for female) or clinically significant laboratory abnormalities
Serum potassium value ≤3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value ≥140 mg/dL.
History or symptoms of significant neurological disease
Unstable concurrent disease: eg uncontrolled Thyroid disease or other endocrine diseases, gastrointestinal uncontrolled disease, uncontrolled immune diseases
Renal impairment.
Patients with abnormal alanine aminotransferase and/ or aspartate aminotransferase and/or bilirubin
Current or chronic history of liver disease, or known hepatic or biliary abnormalities and patients receiving treatment with any drug known to have a well defined potential for hepatotoxicity before Study entry
Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently
History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
Any recent participation to a clinical Study with other investigational drug

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

CHF6001 DOSE1

CHF6001 DOSE2

CHF6001 DOSE3

CHF6001 DOSE4

Matched placebo

Budesonide

Arm Description

DOSE1

DOSE2

DOSE3

DOSE4

placebo control

Budesonide DPI 800µg

Outcomes

Primary Outcome Measures

Change from baseline in predose morning FEV1 at 12 weeks

overall effect of CHF6001 on change from baseline in predose morning FEV1

Secondary Outcome Measures

Change from baseline in predose morning FEV1 at other timepoints

Change from Baseline

Change from baseline in pre-dose morning IC

Change from Baseline for other lung function parameters

Change from baseline in pre-dose morning FVC

Change from Baseline for other lung function parameters

Change from baseline in TDI focal score

Change of TDI score

Change from baseline in SGRQ score

Change of SGRQ score

Change from baseline in E-RS score

Change of E-RSI score

COPD exacerbation rate over 24 weeks of treatment

exacerbation rate

Time to first COPD exacerbation

Full Information

NCT ID

NCT02986321

First Posted

November 24, 2016

Last Updated

January 25, 2019

Sponsor

Chiesi Farmaceutici S.p.A.

1. Study Identification

Unique Protocol Identification Number

NCT02986321

Brief Title

A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD

Acronym

PIONEER

Official Title

A 24-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo and Active Controlled, Parallel Group, Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF6001 DPI in Patients With COPD on a Background Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

December 15, 2016 (Actual)

Primary Completion Date

October 4, 2017 (Actual)

Study Completion Date

January 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Chiesi Farmaceutici S.p.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the dose-response relationship of different doses of CHF6001 and to identify the optimal dose (s) in terms of benefit/risk ratio for further development in the target patient population.

Detailed Description

This is a phase II, randomized, double-blind, double-dummy, placebo and active controlled multinational, multicenter, dose ranging, 6-arm parallel-group study to identify the optimal dose of CHF6001, PDE4 inhibitor under development, with respect to lung functions and symptoms. After a 2-wk run-in period under formoterol (Oxis Turbohaler®) and rescue salbutamol prn, patients will be randomized to one of the 6 treatment groups. After the randomization, patients will be assessed after 3, 6, 12, 18 and 24 weeks of treatment at clinic/hospital. A follow-up visit will be performed 12 days after the last visit. During the study, patients will report daily symptoms with the EXACT-PRO/E-RS questionnaire, rescue/background medication use and compliance with the study medications. AEs, SAEs and COPD exacerbations will be monitored throughout the study. At randomization and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurement, 12-lead ECG. Symptoms and Health status will be assessed through validated questionnaires. Routine lab analysis and blood biomarkers will be done.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

anti-inflammatory respiratory drug, PDE4 inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1130 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CHF6001 DOSE1

Arm Type

Experimental

Arm Description

DOSE1

Arm Title

CHF6001 DOSE2

Arm Type

Experimental

Arm Description

DOSE2

Arm Title

CHF6001 DOSE3

Arm Type

Experimental

Arm Description

DOSE3

Arm Title

CHF6001 DOSE4

Arm Type

Experimental

Arm Description

DOSE4

Arm Title

Matched placebo

Arm Type

Placebo Comparator

Arm Description

placebo control

Arm Title

Budesonide

Arm Type

Active Comparator

Arm Description

Budesonide DPI 800µg

Intervention Type

Drug

Intervention Name(s)

CHF6001

Other Intervention Name(s)

Dose range finding

Intervention Description

Dose response: Test one of 4 different doses of CHF6001

Intervention Type

Drug

Intervention Name(s)

Budesonide

Other Intervention Name(s)

Active comparator

Intervention Description

active control

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo control

Primary Outcome Measure Information:

Title

Change from baseline in predose morning FEV1 at 12 weeks

Description

overall effect of CHF6001 on change from baseline in predose morning FEV1

Time Frame

week 12

Secondary Outcome Measure Information:

Title

Change from baseline in predose morning FEV1 at other timepoints

Description

Change from Baseline

Time Frame

weeks 3, 6, 18, 24

Title

Change from baseline in pre-dose morning IC

Description

Change from Baseline for other lung function parameters

Time Frame

weeks 3, 6, 12, 18, 24

Title

Change from baseline in pre-dose morning FVC

Description

Change from Baseline for other lung function parameters

Time Frame

weeks 3, 6, 12, 18, 24

Title

Change from baseline in TDI focal score

Description

Change of TDI score

Time Frame

weeks 3, 6, 12, 18, 24

Title

Change from baseline in SGRQ score

Description

Change of SGRQ score

Time Frame

weeks 3, 6, 12, 18, 24

Title

Change from baseline in E-RS score

Description

Change of E-RSI score

Time Frame

weeks 3, 6, 12, 18, 24

Title

COPD exacerbation rate over 24 weeks of treatment

Description

exacerbation rate

Time Frame

24 weeks

Title

Time to first COPD exacerbation

Description

Time to first COPD exacerbation

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: COPD patients Non- childbearing potential or woman permanently sterilized or on one or more highly effective contraception Current/ex smokers (history > 10 pack years) Post bronchodilatator FEV1 >=30% and <=70% predicted normal value and FEV1/FVC ratio <0.7 Documented history of at least 1 moderate or severe exacerbation in the 12 months prior to study entry Symptomatic patients (MMRC score ≥2 and a CAT score ≥10) Patients on daily maintenance therapy with an ICS/LABA . Exclusion Criteria: Diagnosis of asthma or other respiratory disorders Maintenance bronchodilators therapy only (eg LABA alone) Maintenance triple therapy. Occurrence of a moderate or severe COPD exacerbation within 6 weeks prior to study entry or during the run-in period. Patients requiring long term oxygen therapy. Concomitant or recent pulmonary rehabilitation programme Known respiratory disorders other than COPD Lung cancer or a history of lung cancer, active or history of cancer with less than 5 years disease free survival time Hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the excipients Depression, generalised anxiety disorder, suicidal ideation Any clinically significant cardiovascular disease (IM, CHF III/IV; AF not controlled by therapy, etc) within 1 year of study entry Any relevant clinically significant cardiovascular condition, clinically abnormal significant 12-lead ECG (QTcF>450 ms for male and >470 for female) or clinically significant laboratory abnormalities Serum potassium value ≤3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value ≥140 mg/dL. History or symptoms of significant neurological disease Unstable concurrent disease: eg uncontrolled Thyroid disease or other endocrine diseases, gastrointestinal uncontrolled disease, uncontrolled immune diseases Renal impairment. Patients with abnormal alanine aminotransferase and/ or aspartate aminotransferase and/or bilirubin Current or chronic history of liver disease, or known hepatic or biliary abnormalities and patients receiving treatment with any drug known to have a well defined potential for hepatotoxicity before Study entry Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit. Any recent participation to a clinical Study with other investigational drug

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dave Singh

Organizational Affiliation

Medicines Evaluation Unit, Manchester, UK

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32962709

Citation

Singh D, Emirova A, Francisco C, Santoro D, Govoni M, Nandeuil MA. Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study. Respir Res. 2020 Sep 22;21(1):246. doi: 10.1186/s12931-020-01512-y.

Results Reference

derived

Links:

URL

https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005548-32

Description

Study Record on EU Clinical Trials Register including results

Learn more about this trial

A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD

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