<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/NCT04461587</url>
  </required_header>
  <id_info>
    <org_study_id>ML42227</org_study_id>
    <nct_id>NCT04461587</nct_id>
  </id_info>
  <brief_title>Examination of Pirfenidone (Esbriet®) Therapy in Coal Workers' Pneumoconiosis With Pulmonary Fibrosis</brief_title>
  <official_title>Examination of Pirfenidone (Esbriet®) Therapy in Coal Workers' Pneumoconiosis With Pulmonary Fibrosis Associated With Radiographic and Functional Impairment to Examine the Reduction in Progression of Disease, Reduction of Exacerbation Rates and Possible Reduction of Inflammatory Biomarkers as an Index of Clinical Response.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pulmonary Research of Abingdon, LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Pulmonary Research of Abingdon, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Examination of pirfenidone (Esbriet®) therapy in coal workers' pneumoconiosis (black lung)&#xD;
      with pulmonary fibrosis (scarring of the lung).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Examination of pirfenidone (Esbriet®) therapy in coal workers' pneumoconiosis with pulmonary&#xD;
      fibrosis associated with radiographic and functional impairment to examine the reduction in&#xD;
      progression of disease, reduction of exacerbation rates and possible reduction of&#xD;
      inflammatory biomarkers as an index of clinical response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Actual">November 16, 2022</completion_date>
  <primary_completion_date type="Actual">November 10, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open label interventional study observing US FDA approved Esbriet (for Interstitial Pulmonary Fibrosis) in Coal Workers' Pneumoconiosis patients with pulmonary fibrosis.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Forced Vital Capacity (FVC)</measure>
    <time_frame>12 months minimum</time_frame>
    <description>Primary objective for this study is to determine the rate of decline ( relative change in FVC (% and ml) in patients with coal workers' pneumoconiosis (Black Lung) with pulmonary fibrosis (CWP/PMF) during treatment with pirfenidone (Esbriet®).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Forced Expiratory Volume in 1 second (FEV1)</measure>
    <time_frame>12 months minimum</time_frame>
    <description>rate of decline (relative change in % and ml )of FEV1 compared to baseline assessments established at enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diffusing capacity of the lung for carbon monoxide (DLCO)</measure>
    <time_frame>12 months minimum</time_frame>
    <description>rate of decline (relative change in %) of DLCO compared to baseline assessments established at enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 minute walk test</measure>
    <time_frame>12 months minimum</time_frame>
    <description>rate of decline of 6 minute walk test compared to baseline assessments established at enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chest CT</measure>
    <time_frame>12 months</time_frame>
    <description>Chest CT scans will be reviewed to determine if radiographic progression occurs during therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory biomarkers</measure>
    <time_frame>12 months minimum</time_frame>
    <description>The reduction of inflammatory biomarkers (Interleukin-6 [IL-6], Transforming Growth Factor Beta 1 [TGF-β 1] and Tumor Necrosis Factor Alpha [TNF-α]) and the potential reduction correlation with change in lung function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>St. George's Respiratory Questionnaire (SGRQ)</measure>
    <time_frame>12 months minimum</time_frame>
    <description>Change in total score compared to baseline. Total score summarizes the impact of the disease on overall health status. Scores range from 0 - 100, with higher scores indicating more limitations.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Rates of Respiratory Exacerbation</measure>
    <time_frame>12 months minimum</time_frame>
    <description>Change in exacerbation rate compared to 12 months prior to enrollment, including respiratory-related hospitalizations.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Coal Workers' Pneumoconiosis (Complicated)</condition>
  <arm_group>
    <arm_group_label>Pirfenidone [Esbriet]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pirfenidone recommended daily dose for patients is 801 mg three times a day with food, for a total of 2403 mg/day. Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/day over a 14day period as follows:&#xD;
Days 1 to 7: a dose of 267 mg administered three times a day (801 mg/day)&#xD;
Days 8 to 14: a dose of 534 mg administered three times a day (1602 mg/day)&#xD;
Day 15 onward: a dose of 801 mg administered three times a day (2403 mg/day) It will be provided in 267mg capsules. Treatment will be for a minimum of 12 months. Treatment duration will continue until last patient enrolled received 12 months of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pirfenidone</intervention_name>
    <description>see previous entries</description>
    <arm_group_label>Pirfenidone [Esbriet]</arm_group_label>
    <other_name>Esbriet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Able and willing to provide informed consent and to comply with study protocol&#xD;
&#xD;
          -  2. Coal miners between the ages 40 to 79 years of age at visit 1with a minimum of 15&#xD;
             years in a coal mining environment&#xD;
&#xD;
          -  3. Chest CT Scan or Chest Xray (within 6 months) confirming diagnosis of CWP,&#xD;
             complicated black lung disease/progressive massive fibrosis will be recorded. If CT&#xD;
             not available must be obtained at Visit 1.&#xD;
&#xD;
          -  4. Evidence of Loss of lung function defined by decline in FEV1 or FVC or DLCO of 5%&#xD;
             within the past 36 months prior to enrollment.&#xD;
&#xD;
          -  5. FEV1 ≤ 75% or FVC ≤ 80% or DLCO ≤ 70% or abnormal 6MWT with oxygen desaturation of&#xD;
             4% or greater than resting at screening or within past 6 months.&#xD;
&#xD;
          -  6. Former smokers and current smokers will be enrolled if documented evidence of&#xD;
             CWP/PMF is present and meet PFT guidelines. Current smokers will be given smoking&#xD;
             cessation counseling at each visit due to the effect on pirfenidone concentration and&#xD;
             efficacy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. History of prior therapy with Esbriet or Ofev (pirfenidone or nintedanib)&#xD;
&#xD;
          -  2. Recent hospitalization (within 30 days prior to screening) for respiratory&#xD;
             decompensation.&#xD;
&#xD;
          -  3. Patients using monoclonal antibody therapy or immunosuppressive therapy for other&#xD;
             disease process will be excluded, except for the following:&#xD;
&#xD;
               -  Daily prednisone up to 10 mg daily (prescribed for lung disease or rheumatoid&#xD;
                  arthritis) will be permitted. Chronic use for 3 months prior to enrollment will&#xD;
                  be documented.&#xD;
&#xD;
               -  Methotrexate for rheumatoid arthritis will be permitted as long as chronic use&#xD;
                  for 6 months prior to enrollment is documented.&#xD;
&#xD;
          -  4. Elevation of liver function test at screening documenting AST, ALT or total&#xD;
             bilirubin &gt; 3 x ULN or ALP &gt; 2.5 x ULN.&#xD;
&#xD;
          -  5. Patients who have other pulmonary pathology such as lung cancer, active&#xD;
             tuberculosis or atypical mycobacterial infection requiring treatment.&#xD;
&#xD;
          -  6. Patients with recurrent malignancy requiring chemotherapy or radiation therapy.&#xD;
             Individuals with a prior diagnosis of localized skin cancer, prostate cancer,&#xD;
             localized bladder cancer will not be excluded unless undergoing active treatment.&#xD;
             Patients with a prior diagnosis of malignancy treated greater than 5 years ago will be&#xD;
             considered for enrollment.&#xD;
&#xD;
          -  7. History of alcohol or drug abuse that would impair or risk the patient's full&#xD;
             participation in the drug study in the opinion of the investigator&#xD;
&#xD;
          -  8. Use of any investigational therapy within 4 weeks of enrollment.&#xD;
&#xD;
          -  9. Individuals with clinically significant unstable cardiac disease (ejection fraction&#xD;
             ≤35%) or complex arrhythmias per PI discretion. Chronic atrial fibrillation will be&#xD;
             permitted if heart rate is controlled. Historical values of ejection fraction will be&#xD;
             accepted.&#xD;
&#xD;
          -  10. Individuals with poorly controlled diabetes per PI discretion (Hemoglobin A1c &gt;9).&#xD;
             Historical values will be accepted.&#xD;
&#xD;
          -  11. Pregnancy or lactation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emory Robinette, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pulmonary Research of Abingdon, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pulmonary Research of Abingdon, LLC</name>
      <address>
        <city>Abingdon</city>
        <state>Virginia</state>
        <zip>24210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>March 20, 2023</last_update_submitted>
  <last_update_submitted_qc>March 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Black Lung</keyword>
  <keyword>Black Lung Disease</keyword>
  <keyword>Coal Miner's Lung</keyword>
  <keyword>Coal Worker's Pneumoconiosis</keyword>
  <keyword>Coalworker's Pneumoconiosis</keyword>
  <keyword>Pneumoconiosis, Coal Worker's</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Pneumoconiosis</mesh_term>
    <mesh_term>Anthracosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pirfenidone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04461587
org study id: ML42227
nct id: NCT04461587
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Examination of pirfenidone (Esbriet®) therapy in coal workers' pneumoconiosis (black lung)
      with pulmonary fibrosis (scarring of the lung).
Examination of pirfenidone (Esbriet®) therapy in coal workers' pneumoconiosis with pulmonary
      fibrosis associated with radiographic and functional impairment to examine the reduction in
      progression of disease, reduction of exacerbation rates and possible reduction of
      inflammatory biomarkers as an index of clinical response.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open label interventional study observing US FDA approved Esbriet (for Interstitial Pulmonary Fibrosis) in Coal Workers' Pneumoconiosis patients with pulmonary fibrosis.
primary purpose: Treatment
masking: None (Open Label)
measure: Forced Vital Capacity (FVC)
time frame: 12 months minimum
description: Primary objective for this study is to determine the rate of decline ( relative change in FVC (% and ml) in patients with coal workers' pneumoconiosis (Black Lung) with pulmonary fibrosis (CWP/PMF) during treatment with pirfenidone (Esbriet®).
measure: Forced Expiratory Volume in 1 second (FEV1)
time frame: 12 months minimum
description: rate of decline (relative change in % and ml )of FEV1 compared to baseline assessments established at enrollment.
measure: Diffusing capacity of the lung for carbon monoxide (DLCO)
time frame: 12 months minimum
description: rate of decline (relative change in %) of DLCO compared to baseline assessments established at enrollment.
measure: 6 minute walk test
time frame: 12 months minimum
description: rate of decline of 6 minute walk test compared to baseline assessments established at enrollment.
measure: Chest CT
time frame: 12 months
description: Chest CT scans will be reviewed to determine if radiographic progression occurs during therapy.
measure: Inflammatory biomarkers
time frame: 12 months minimum
description: The reduction of inflammatory biomarkers (Interleukin-6 [IL-6], Transforming Growth Factor Beta 1 [TGF-β 1] and Tumor Necrosis Factor Alpha [TNF-α]) and the potential reduction correlation with change in lung function
measure: St. George's Respiratory Questionnaire (SGRQ)
time frame: 12 months minimum
description: Change in total score compared to baseline. Total score summarizes the impact of the disease on overall health status. Scores range from 0 - 100, with higher scores indicating more limitations.
measure: Rates of Respiratory Exacerbation
time frame: 12 months minimum
description: Change in exacerbation rate compared to 12 months prior to enrollment, including respiratory-related hospitalizations.
arm group label: Pirfenidone [Esbriet]
arm group type: Experimental
description: Pirfenidone recommended daily dose for patients is 801 mg three times a day with food, for a total of 2403 mg/day. Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/day over a 14day period as follows:
Days 1 to 7: a dose of 267 mg administered three times a day (801 mg/day)
Days 8 to 14: a dose of 534 mg administered three times a day (1602 mg/day)
Day 15 onward: a dose of 801 mg administered three times a day (2403 mg/day) It will be provided in 267mg capsules. Treatment will be for a minimum of 12 months. Treatment duration will continue until last patient enrolled received 12 months of treatment.
intervention type: Drug
intervention name: Pirfenidone
description: see previous entries
arm group label: Pirfenidone [Esbriet]
other name: Esbriet
criteria: 
gender: All
minimum age: 40 Years
maximum age: 79 Years
healthy volunteers: No
last name: Emory Robinette, MD
role: Principal Investigator
affiliation: Pulmonary Research of Abingdon, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pulmonary Fibrosis
mesh term: Pneumoconiosis
mesh term: Anthracosis
mesh term: Pirfenidone
sharing ipd: Undecided