<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03004417</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-06001AA1-10</org_study_id>
    <secondary_id>2015-005550-35</secondary_id>
    <nct_id>NCT03004417</nct_id>
  </id_info>
  <brief_title>Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SGS S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Chiesi Farmaceutici S.p.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Effect of CHF 6001 on biomarkers of inflammation in induced sputum and in blood, on pulmonary&#xD;
      function and on symptoms benefits in comparison with placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to obtain information on the effects of two doses of CHF6001 on&#xD;
      sputum and blood biomarkers of inflammation in subjects with symptomatic COPD with moderate,&#xD;
      severe airflow limitation and with chronic bronchitis. The efficacy of the treatment will&#xD;
      also be measured using forced oscillometry technique and spirometry. Safety, tolerability and&#xD;
      pharmacokinetics will be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2016</start_date>
  <completion_date type="Actual">December 28, 2017</completion_date>
  <primary_completion_date type="Actual">December 28, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sputum biomarkers</measure>
    <time_frame>Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;</time_frame>
    <description>- 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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sputum biomarkers</measure>
    <time_frame>Predose and end of treatment at Day 32 of each period</time_frame>
    <description>Sputum gene expression analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sputum cell count</measure>
    <time_frame>Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;</time_frame>
    <description>Total cell count&#xD;
Absolute and percent of neutrophils, eosinophils, macrophages and lymphocytes differential cell count.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Biomarkers</measure>
    <time_frame>Change from baseline to Day 32 of each period;</time_frame>
    <description>Blood Biomarkers</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Biomarkers</measure>
    <time_frame>Predose and end of treatment at Day 32 of each period</time_frame>
    <description>Blood gene expression analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lung function: Spirometry</measure>
    <time_frame>Change from baseline to Day 20 Day 26 and 32 of each period</time_frame>
    <description>pre-dose FEV1, FVC and IC</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lung function: Oscillometry</measure>
    <time_frame>Change from baseline to Day 32 of each period</time_frame>
    <description>R5, R19, R5-R19, X5, EFL index</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK: AUC0-12h,ss</measure>
    <time_frame>on Day 32 (steady state) of each period.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK: Cmax</measure>
    <time_frame>on Day 32 (steady state) of each period.</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>CHF 6001 Dose1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHF 6001 Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF 6001 Dose1</intervention_name>
    <description>CHF 6001 plus placebo</description>
    <arm_group_label>CHF 6001 Dose1</arm_group_label>
    <other_name>CHF 6001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHF 6001 Dose2</intervention_name>
    <description>CHF 6001 only (high dose)</description>
    <arm_group_label>CHF 6001 Dose 2</arm_group_label>
    <other_name>CHF 6001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo only</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female aged ≥40 years&#xD;
&#xD;
          -  A female is eligible to enter the study if she is of non-childbearing potential i.e.&#xD;
             physiologically incapable of becoming pregnant Women physiologically capable of&#xD;
             becoming pregnant (i.e. women of childbearing potential) are eligible to enter the&#xD;
             study if they have negative pregnancy test at screening and agree to use one or more&#xD;
             of the following highly effective contraceptive measures&#xD;
&#xD;
          -  Subjects with an established diagnosis of COPD (according to GOLD guidelines, update&#xD;
             2015) at least 12 months prior to the screening visit&#xD;
&#xD;
          -  With a smoking history of at least 10 pack-years [pack-years=number of cigarettes per&#xD;
             day x number of years/20]. Current and ex- smokers are eligible. With a BMI in the&#xD;
             range of 18-35 Kg/m2 With a post-bronchodilator FEV1 ≥30% and ≤70%&#xD;
&#xD;
          -  Subjects must be receiving daily maintenance with triple therapy (ICS plus LABA plus&#xD;
             LAMA) at stable dose and dosing regimen, for at least 2 months prior to screening&#xD;
&#xD;
          -  With a history of chronic bronchitis defined as chronic cough and sputum production&#xD;
             for more than three months per year for two or more years and known as 'spontaneous&#xD;
             sputum producer' subject&#xD;
&#xD;
          -  Subjects must be symptomatic at screening defined as having a CAT score ≥10&#xD;
&#xD;
          -  Subjects must be able to be trained to correctly use the DPI inhalers and They must&#xD;
             have a cooperative attitude and ability to perform the required outcome measurements&#xD;
             (e.g. spirometry testing, induced sputum...).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating female subject&#xD;
&#xD;
          -  Subjects with a current diagnosis of asthma&#xD;
&#xD;
          -  Subjects with a moderate or severe COPD exacerbation [i.e. resulting in the use of&#xD;
             systemic (oral/IV/IM corticosteroids) and/or antibiotics or in hospitalisation] or a&#xD;
             lower respiratory tract infection within 6 weeks prior to study entry or during the&#xD;
             screening period&#xD;
&#xD;
          -  Subjects on maintenance bronchodilators therapy only (LABA alone, LAMA alone, dual&#xD;
             LABA/LAMA alone) or maintenance dual therapy only (ICS/LABA or ICS plus LAMA) within 2&#xD;
             months prior to study entry&#xD;
&#xD;
          -  Subjects on PDE4 inhibitors (e.g. roflumilast) within 2 months prior to study entry&#xD;
&#xD;
          -  Subjects requiring long-term (at least 12 hours daily) oxygen therapy for chronic&#xD;
             hypoxemia; participating to a pulmonary rehabilitation programme or completing such a&#xD;
             programme within the last 6 weeks prior to study entry&#xD;
&#xD;
          -  Subjects with known respiratory disorders other than COPD...&#xD;
&#xD;
          -  Subjects have lung cancer or a history of lung cancer or with active cancer or a&#xD;
             history of cancer (other than lung) with less than 5 years disease free survival time&#xD;
&#xD;
          -  Subjects with a known history of hypersensitivity to beta2-agonist, PDE4 inhibitors or&#xD;
             any of the excipients contained in any of the formulations used in the trial&#xD;
&#xD;
          -  Subjects with a diagnosis of depression associated with suicidal ideation or behaviour&#xD;
             or with a diagnosis of generalised anxiety disorder that in the investigator's opinion&#xD;
             would place the patient at risk&#xD;
&#xD;
          -  Subjects who have known history of clinically significant cardiovascular conditions&#xD;
             such as, but not limited to, unstable or acute ischemic heart disease within one year&#xD;
             prior to study entry, NYHA Class III/IV heart failure, known history of sustained and&#xD;
             non-sustained cardiac arrhythmias or history of atrial fibrillation diagnosed in the&#xD;
             last 6 months prior to study entry and not controlled with therapy rate control&#xD;
             strategy&#xD;
&#xD;
          -  Subjects who have unstable concurrent disease&#xD;
&#xD;
          -  Subjects with clinically significant laboratory abnormalities&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones)&#xD;
&#xD;
          -  Subjects receiving treatment with any drug known to have a well-defined potential for&#xD;
             hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3&#xD;
             months prior to the study entry and during the screening period&#xD;
&#xD;
          -  Subjects have experienced excessive weight loss recently (which cannot be explained by&#xD;
             the natural course of COPD or known background conditions).&#xD;
&#xD;
          -  Subjects with a history of alcohol abuse and/or substance/drug abuse within 12 months&#xD;
             prior to screening visit&#xD;
&#xD;
          -  Subjects having received any other investigational drug within the preceding 30 days&#xD;
             (60 days for biologics).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dave Singh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MEU - Manchester - UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medicines Evaluation Unit Ltd</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.clinicaltrialsregister.eu/ctr-search/trial/2015-005550-35</url>
    <description>Study Record on EU Clinical Trials Register including results</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>32197620</PMID>
  </reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31399091</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03004417
org study id: CCD-06001AA1-10
secondary id: 2015-005550-35
nct id: NCT03004417
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Sputum biomarkers
time frame: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
description: - 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.
measure: Sputum biomarkers
time frame: Predose and end of treatment at Day 32 of each period
description: Sputum gene expression analysis
measure: Sputum cell count
time frame: Change from baseline to end of treatment (mean Day 20, 26 and 32 values) at each period;
description: Total cell count
Absolute and percent of neutrophils, eosinophils, macrophages and lymphocytes differential cell count.
measure: Blood Biomarkers
time frame: Change from baseline to Day 32 of each period;
description: Blood Biomarkers
measure: Blood Biomarkers
time frame: Predose and end of treatment at Day 32 of each period
description: Blood gene expression analysis
measure: Lung function: Spirometry
time frame: Change from baseline to Day 20 Day 26 and 32 of each period
description: pre-dose FEV1, FVC and IC
measure: Lung function: Oscillometry
time frame: Change from baseline to Day 32 of each period
description: R5, R19, R5-R19, X5, EFL index
measure: PK: AUC0-12h,ss
time frame: on Day 32 (steady state) of each period.
measure: PK: Cmax
time frame: on Day 32 (steady state) of each period.
arm group label: CHF 6001 Dose1
arm group type: Experimental
description: CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.
arm group label: CHF 6001 Dose 2
arm group type: Experimental
description: CHF6001 via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo via NEXThaler® dry powder inhaler (DPI), b.i.d. for 32 consecutive days.
intervention type: Drug
intervention name: CHF 6001 Dose1
description: CHF 6001 plus placebo
arm group label: CHF 6001 Dose1
other name: CHF 6001
intervention type: Drug
intervention name: CHF 6001 Dose2
description: CHF 6001 only (high dose)
arm group label: CHF 6001 Dose 2
other name: CHF 6001
intervention type: Other
intervention name: Placebo
description: Placebo only
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Dave Singh, MD
role: Principal Investigator
affiliation: MEU - Manchester - UK
facility: 
country: United Kingdom
url: http://www.clinicaltrialsregister.eu/ctr-search/trial/2015-005550-35
description: Study Record on EU Clinical Trials Register including results
citation: 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
citation: 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
responsible party type: Sponsor
sharing ipd: No