Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD

NCT03004417 | Completed Phase 2

• 2 other identifiers: CCD-06001AA1-102015-005550-35
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Effect of CHF 6001 on biomarkers of inflammation in induced sputum and in blood, on pulmonary function and on symptoms benefits in comparison with placebo.

Conditions

COPD

Outcome Measures

Primary Outcomes (9)

• Sputum biomarkers

  \- IL-6, IL-8 (CXCL-8), IL-1β, TNF-α, MIP1β, MCP-1, MyeloPerOxidase (MPO), Neutrophil Elastase (NE), MMP9, Acetyl-proline-glycine-proline (AcPGP), leukotriene B4 (LTB4), eosinophil cationic protein (ECP) and α2-macroglobulin.

  Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;

• Sputum biomarkers

  Sputum gene expression analysis

  Predose and end of treatment at Day 32 of each period

• Sputum cell count

  * Total cell count * Absolute and percent of neutrophils, eosinophils, macrophages and lymphocytes differential cell count.

  Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;

• Blood Biomarkers

  Blood Biomarkers

  Change from baseline to Day 32 of each period;

• Blood Biomarkers

  Blood gene expression analysis

  Predose and end of treatment at Day 32 of each period

• Lung function: Spirometry

  pre-dose FEV1, FVC and IC

  Change from baseline to Day 20 Day 26 and 32 of each period

• Lung function: Oscillometry

  R5, R19, R5-R19, X5, EFL index

  Change from baseline to Day 32 of each period

• PK: AUC0-12h,ss

  on Day 32 (steady state) of each period.

• PK: Cmax

  on Day 32 (steady state) of each period.

Study Arms (3)

CHF 6001 Dose1

EXPERIMENTAL

CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.

Drug: CHF 6001 Dose1

CHF 6001 Dose 2

EXPERIMENTAL

CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.

Drug: CHF 6001 Dose2

Placebo

PLACEBO COMPARATOR

Matching placebo via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.

Other: Placebo

Interventions

CHF 6001 Dose1 DRUG

CHF 6001 plus placebo

Also known as: CHF 6001

CHF 6001 Dose1

CHF 6001 Dose2 DRUG

CHF 6001 only (high dose)

Also known as: CHF 6001

CHF 6001 Dose 2

Placebo OTHER

Placebo only

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female aged ≥40 years
• A female is eligible to enter the study if she is of non-childbearing potential i.e. physiologically incapable of becoming pregnant Women physiologically capable of becoming pregnant (i.e. women of childbearing potential) are eligible to enter the study if they have negative pregnancy test at screening and agree to use one or more of the following highly effective contraceptive measures
• Subjects with an established diagnosis of COPD (according to GOLD guidelines, update 2015) at least 12 months prior to the screening visit
• With a smoking history of at least 10 pack-years \[pack-years=number of cigarettes per day x number of years/20\]. Current and ex- smokers are eligible. With a BMI in the range of 18-35 Kg/m2 With a post-bronchodilator FEV1 ≥30% and ≤70%
• Subjects must be receiving daily maintenance with triple therapy (ICS plus LABA plus LAMA) at stable dose and dosing regimen, for at least 2 months prior to screening
• With a history of chronic bronchitis defined as chronic cough and sputum production for more than three months per year for two or more years and known as 'spontaneous sputum producer' subject
• Subjects must be symptomatic at screening defined as having a CAT score ≥10
• Subjects must be able to be trained to correctly use the DPI inhalers and They must have a cooperative attitude and ability to perform the required outcome measurements (e.g. spirometry testing, induced sputum...).

You may not qualify if:

• Pregnant or lactating female subject
• Subjects with a current diagnosis of asthma
• Subjects with a moderate or severe COPD exacerbation \[i.e. resulting in the use of systemic (oral/IV/IM corticosteroids) and/or antibiotics or in hospitalisation\] or a lower respiratory tract infection within 6 weeks prior to study entry or during the screening period
• Subjects on maintenance bronchodilators therapy only (LABA alone, LAMA alone, dual LABA/LAMA alone) or maintenance dual therapy only (ICS/LABA or ICS plus LAMA) within 2 months prior to study entry
• Subjects on PDE4 inhibitors (e.g. roflumilast) within 2 months prior to study entry
• Subjects requiring long-term (at least 12 hours daily) oxygen therapy for chronic hypoxemia; participating to a pulmonary rehabilitation programme or completing such a programme within the last 6 weeks prior to study entry
• Subjects with known respiratory disorders other than COPD...
• Subjects have lung cancer or a history of lung cancer or with active cancer or a history of cancer (other than lung) with less than 5 years disease free survival time
• Subjects with a known history of hypersensitivity to beta2-agonist, PDE4 inhibitors or any of the excipients contained in any of the formulations used in the trial
• Subjects with a diagnosis of depression associated with suicidal ideation or behaviour or with a diagnosis of generalised anxiety disorder that in the investigator's opinion would place the patient at risk
• Subjects who have known history of clinically significant cardiovascular conditions such as, but not limited to, unstable or acute ischemic heart disease within one year prior to study entry, NYHA Class III/IV heart failure, known history of sustained and non-sustained cardiac arrhythmias or history of atrial fibrillation diagnosed in the last 6 months prior to study entry and not controlled with therapy rate control strategy
• Subjects who have unstable concurrent disease
• Subjects with clinically significant laboratory abnormalities
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months prior to the study entry and during the screening period

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• SGS S.A.: collaborator

Study Sites (1)

Medicines Evaluation Unit Ltd

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (4)

• Govoni M, Bassi M, Vezzoli S, Lucci G, Emirova A, Nandeuil MA, Petruzzelli S, Jellema GL, Afolabi EK, Colgan B, Leaker B, Kornmann O, Beeh KM, Watz H, Singh D. Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis. Respir Res. 2020 Mar 20;21(1):72. doi: 10.1186/s12931-020-1329-y.

  PMID: 32197620 BACKGROUND

• Singh D, Beeh KM, Colgan B, Kornmann O, Leaker B, Watz H, Lucci G, Geraci S, Emirova A, Govoni M, Nandeuil MA. Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respir Res. 2019 Aug 9;20(1):180. doi: 10.1186/s12931-019-1142-7.

  PMID: 31399091 RESULT

• Govoni M, Bassi M, Santoro D, Donegan S, Singh D. Serum IL-8 as a Determinant of Response to Phosphodiesterase-4 Inhibition in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2023 Sep 1;208(5):559-569. doi: 10.1164/rccm.202301-0071OC.

  PMID: 37192443 DERIVED

• Singh D, Watz H, Beeh KM, Kornmann O, Leaker B, Colgan B, Lucci G, Emirova A, Nandeuil MA, Santoro D, Balzano D, Govoni M. COPD sputum eosinophils: relationship to blood eosinophils and the effect of inhaled PDE4 inhibition. Eur Respir J. 2020 Aug 6;56(2):2000237. doi: 10.1183/13993003.00237-2020. Print 2020 Aug.

  PMID: 32341106 DERIVED

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dave Singh, MD

  MEU - Manchester - UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 28, 2016
• Study Start: October 31, 2016
• Primary Completion: December 28, 2017
• Study Completion: December 28, 2017
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)