COPDPhase 2NCT03004417
Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD
A Phase 2 study testing CHF 6001 Dose1 and CHF 6001 Dose2 in people with COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD
- What is being tested?
- CHF 6001 Dose1 and CHF 6001 Dose2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Oct 2016to 28 Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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...).
Who cannot join
- 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
Show all 18Show fewer
- 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
- Subjects have experienced excessive weight loss recently (which cannot be explained by the natural course of COPD or known background conditions).
- Subjects with a history of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit
- Subjects having received any other investigational drug within the preceding 30 days (60 days for biologics).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind,Placebo Controlled, Repeated Dose, Three-way Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD
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.
Read the detailed description
The purpose of this study is to obtain information on the effects of two doses of CHF6001 on sputum and blood biomarkers of inflammation in subjects with symptomatic COPD with moderate, severe airflow limitation and with chronic bronchitis. The efficacy of the treatment will also be measured using forced oscillometry technique and spirometry. Safety, tolerability and pharmacokinetics will be evaluated.
- Conditions
- COPD
- Being tested
- CHF 6001 Dose1, CHF 6001 Dose2, Placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHF 6001 Dose1Drug
Also called CHF 6001
CHF 6001 plus placebo
CHF 6001 Dose2Drug
Also called CHF 6001
CHF 6001 only (high dose)
PlaceboOther
Placebo only
| Study group | Role | What they receive |
|---|---|---|
| CHF 6001 Dose1 | Experimental | CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. Receives: Drug: CHF 6001 Dose1 |
| CHF 6001 Dose 2 | Experimental | CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. Receives: Drug: CHF 6001 Dose2 |
| Placebo | Placebo comparator | Matching placebo via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
Sputum biomarkers
Sputum gene expression analysis
Measured: 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.
Measured: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
Blood Biomarkers
Blood Biomarkers
Measured: Change from baseline to Day 32 of each period;
Blood Biomarkers
Blood gene expression analysis
Measured: Predose and end of treatment at Day 32 of each period
Lung function: Spirometry
pre-dose FEV1, FVC and IC
Measured: Change from baseline to Day 20 Day 26 and 32 of each period
Lung function: Oscillometry
R5, R19, R5-R19, X5, EFL index
Measured: Change from baseline to Day 32 of each period
PK: AUC0-12h,ss
Measured: on Day 32 (steady state) of each period.
PK: Cmax
Measured: on Day 32 (steady state) of each period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2016 (estimated)
- Study start31 Oct 2016
- Primary completion28 Dec 2017
- Study completion28 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Responsible party
- Sponsor
- Investigators
- Dave Singh, MD, Principal investigator, MEU - Manchester - UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03004417
- Sponsor's protocol ID
- CCD-06001AA1-10
- Other IDs
- 2015-005550-35, 2015
- Status last verified
- Jul 2020
- First submitted
- 2 Dec 2016
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 32197620Singh 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.
PubMed 31399091Govoni 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.
PubMed 37192443Singh 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.
PubMed 32341106
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind,Placebo Controlled, Repeated Dose, Three-way Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD
- ClinicalTrials.gov ID
- NCT03004417
- Acronym / sponsor ID
- CCD-06001AA1-10
- Conditions
- COPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Study start
- 31 Oct 2016 (actual)
- Primary completion
- 28 Dec 2017 (actual)
- Study completion
- 28 Dec 2017 (actual)
- First posted
- 28 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The purpose of this study is to obtain information on the effects of two doses of CHF6001 on sputum and blood biomarkers of inflammation in subjects with symptomatic COPD with moderate, severe airflow limitation and with chronic bronchitis. The efficacy of the treatment will also be measured using forced oscillometry technique and spirometry. Safety, tolerability and pharmacokinetics will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CHF 6001 Dose1 | Experimental | Drug: CHF 6001 Dose1CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. |
| CHF 6001 Dose 2 | Experimental | Drug: CHF 6001 Dose2CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. |
| Placebo | Placebo comparator | Other: PlaceboMatching placebo via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CHF 6001 Dose1Also: CHF 6001CHF 6001 plus placebo | Drug | CHF 6001 Dose1 |
| CHF 6001 Dose2Also: CHF 6001CHF 6001 only (high dose) | Drug | CHF 6001 Dose 2 |
| PlaceboPlacebo only | Other | Placebo |
Primary outcome
Sputum biomarkers
Time frame: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
- 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.
Sputum biomarkers
Time frame: Predose and end of treatment at Day 32 of each period
Sputum gene expression analysis
Sputum cell count
Time frame: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
* Total cell count * Absolute and percent of neutrophils, eosinophils, macrophages and lymphocytes differential cell count.
Blood Biomarkers
Time frame: Change from baseline to Day 32 of each period;
Blood Biomarkers
Blood Biomarkers
Time frame: Predose and end of treatment at Day 32 of each period
Blood gene expression analysis
Lung function: Spirometry
Time frame: Change from baseline to Day 20 Day 26 and 32 of each period
pre-dose FEV1, FVC and IC
Lung function: Oscillometry
Time frame: Change from baseline to Day 32 of each period
R5, R19, R5-R19, X5, EFL index
PK: AUC0-12h,ss
Time frame: on Day 32 (steady state) of each period.
PK: Cmax
Time frame: on Day 32 (steady state) of each period.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Background: PubMed 32197620Govoni 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.
- Results publication: PubMed 31399091Singh 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.
- Derived from this study: PubMed 37192443Govoni 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.
- Derived from this study: PubMed 32341106Singh 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.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dave Singh, MD principal investigator
MEU - Manchester - UK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CHF 6001 Dose1 and CHF 6001 Dose2 in people with COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sputum biomarkers (time frame: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03004417, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.