Examination of Pirfenidone (Esbriet®) Therapy in Coal Workers' Pneumoconiosis With Pulmonary Fibrosis

Study Overview
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Brief Summary
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Examination of pirfenidone (Esbriet®) therapy in coal workers' pneumoconiosis (black lung) with pulmonary fibrosis (scarring of the lung).

Detailed Description
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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
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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.

Conditions
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Coal Workers' Pneumoconiosis (Complicated)

Intervention / Treatment
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* Drug: Pirfenidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Able and willing to provide informed consent and to comply with study protocol 2. Coal miners between the ages 40 to 79 years of age at visit 1with a minimum of 15 years in a coal mining environment 3. Chest CT Scan or Chest Xray (within 6 months) confirming diagnosis of CWP, complicated black lung disease/progressive massive fibrosis will be recorded. If CT not available must be obtained at Visit 1. 4. Evidence of Loss of lung function defined by decline in FEV1 or FVC or DLCO of 5% within the past 36 months prior to enrollment. 5. FEV1 ≤ 75% or FVC ≤ 80% or DLCO ≤ 70% or abnormal 6MWT with oxygen desaturation of 4% or greater than resting at screening or within past 6 months. 6. Former smokers and current smokers will be enrolled if documented evidence of CWP/PMF is present and meet PFT guidelines. Current smokers will be given smoking cessation counseling at each visit due to the effect on pirfenidone concentration and efficacy. Exclusion Criteria: 1. History of prior therapy with Esbriet or Ofev (pirfenidone or nintedanib) 2. Recent hospitalization (within 30 days prior to screening) for respiratory decompensation. 3. Patients using monoclonal antibody therapy or immunosuppressive therapy for other disease process will be excluded, except for the following: Daily prednisone up to 10 mg daily (prescribed for lung disease or rheumatoid arthritis) will be permitted. Chronic use for 3 months prior to enrollment will be documented. Methotrexate for rheumatoid arthritis will be permitted as long as chronic use for 6 months prior to enrollment is documented. 4. Elevation of liver function test at screening documenting AST, ALT or total bilirubin > 3 x ULN or ALP > 2.5 x ULN. 5. Patients who have other pulmonary pathology such as lung cancer, active tuberculosis or atypical mycobacterial infection requiring treatment. 6. Patients with recurrent malignancy requiring chemotherapy or radiation therapy. Individuals with a prior diagnosis of localized skin cancer, prostate cancer, localized bladder cancer will not be excluded unless undergoing active treatment. Patients with a prior diagnosis of malignancy treated greater than 5 years ago will be considered for enrollment. 7. History of alcohol or drug abuse that would impair or risk the patient's full participation in the drug study in the opinion of the investigator 8. Use of any investigational therapy within 4 weeks of enrollment. 9. Individuals with clinically significant unstable cardiac disease (ejection fraction ≤35%) or complex arrhythmias per PI discretion. Chronic atrial fibrillation will be permitted if heart rate is controlled. Historical values of ejection fraction will be accepted. 10. Individuals with poorly controlled diabetes per PI discretion (Hemoglobin A1c >9). Historical values will be accepted. 11. Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label interventional study observing US FDA approved Esbriet (for Interstitial Pulmonary Fibrosis) in Coal Workers' Pneumoconiosis patients with pulmonary fibrosis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pirfenidone [Esbriet]<br>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. | Drug: Pirfenidone<br>* see previous entries<br>* Other names: Esbriet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity (FVC) | 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®). | 12 months minimum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 second (FEV1) | rate of decline (relative change in % and ml )of FEV1 compared to baseline assessments established at enrollment. | 12 months minimum | 
| Diffusing capacity of the lung for carbon monoxide (DLCO) | rate of decline (relative change in %) of DLCO compared to baseline assessments established at enrollment. | 12 months minimum | 
| 6 minute walk test | rate of decline of 6 minute walk test compared to baseline assessments established at enrollment. | 12 months minimum | 
| Chest CT | Chest CT scans will be reviewed to determine if radiographic progression occurs during therapy. | 12 months | 
| Inflammatory biomarkers | 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 | 12 months minimum | 
| St. George's Respiratory Questionnaire (SGRQ) | 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. | 12 months minimum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Black Lung, Black Lung Disease, Coal Miner's Lung, Coal Worker's Pneumoconiosis, Coalworker's Pneumoconiosis, Pneumoconiosis, Coal Worker's