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

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

Sponsors

Lead sponsor: Chiesi Farmaceutici S.p.A.

Source Chiesi Farmaceutici S.p.A.
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.

Overall Status Completed
Start Date December 15, 2016
Completion Date January 9, 2018
Primary Completion Date October 4, 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from baseline in predose morning FEV1 at 12 weeks week 12
Secondary Outcome
Measure Time Frame
Change from baseline in predose morning FEV1 at other timepoints weeks 3, 6, 18, 24
Change from baseline in pre-dose morning IC weeks 3, 6, 12, 18, 24
Change from baseline in pre-dose morning FVC weeks 3, 6, 12, 18, 24
Change from baseline in TDI focal score weeks 3, 6, 12, 18, 24
Change from baseline in SGRQ score weeks 3, 6, 12, 18, 24
Change from baseline in E-RS score weeks 3, 6, 12, 18, 24
COPD exacerbation rate over 24 weeks of treatment 24 weeks
Time to first COPD exacerbation 24 weeks
Enrollment 1130
Condition
Intervention

Intervention type: Drug

Intervention name: CHF6001

Description: Dose response: Test one of 4 different doses of CHF6001

Other name: Dose range finding

Intervention type: Drug

Intervention name: Budesonide

Description: active control

Arm group label: Budesonide

Other name: Active comparator

Intervention type: Drug

Intervention name: Placebo

Description: placebo control

Arm group label: Matched placebo

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

Gender: All

Minimum age: 40 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Dave Singh Principal Investigator Medicines Evaluation Unit, Manchester, UK
Verification Date

January 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Arm group label: CHF6001 DOSE1

Arm group type: Experimental

Description: DOSE1

Arm group label: CHF6001 DOSE2

Arm group type: Experimental

Description: DOSE2

Arm group label: CHF6001 DOSE3

Arm group type: Experimental

Description: DOSE3

Arm group label: CHF6001 DOSE4

Arm group type: Experimental

Description: DOSE4

Arm group label: Matched placebo

Arm group type: Placebo Comparator

Description: placebo control

Arm group label: Budesonide

Arm group type: Active Comparator

Description: Budesonide DPI 800µg

Acronym PIONEER
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov