Pirfenidone for the Reduction of Metabolic, Inflammatory and Fibrogenic Activity in Complicated Silicosis

NCT05118256 | Unknown Phase 2

• 1 other identifier: FUN-PIR-2020-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Silicosis is one of the leading causes of occupational respiratory disease worldwide. It is due to inhalation of respirable crystalline silica and can lead to progressive massive fibrosis (PMF), respiratory failure, and death. It is estimated that it causes more than 10,000 deaths a year worldwide, mainly in developing countries, although the level of underdiagnosis is high. In developed countries the incidence of the disease has been progressively decreasing in recent years, mainly due to the implementation of effective prevention measures, better occupational health surveillance systems and the displacement of mining activity to other countries, in a way that in the United Kingdom 216 cases were reported from 1996 to 2017. At the moment, there is no curative treatment for the disease, and the only therapeutic option is lung transplantation (when the disease evolves to PMF and subsequent respiratory failure). Meanwhile, the only accepted treatment is supportive treatment, with the administration of oxygen therapy in case of respiratory failure, early treatment of respiratory infections, vaccinations and respiratory rehabilitation. In recent years, molecules with antifibrogenic capacity have been developed and have demonstrated their ability to decrease pulmonary fibrogenic activity in diseases such as Idiopathic Pulmonary Fibrosis (IPF). This has been a milestone in the treatment of this disease and, therefore, its possible application to other diseases that share fibrogenic mechanisms with IPF, as PMF. The two molecules with the most clinical experience and approved for IPF are nintedanib and pirfenidone. The antifibrotic properties of pirfenidone have raised great expectations and many clinical trials are currently being carried out in other lung diseases that cause fibrosis, that is why we decide to study the efficacy of pirfenidone in reducing metabolic, inflammatory, and fibrogenic lung disease in patients with artificial stone silicosis and progressive massive fibrosis (PMF).

Conditions

Silicosis; Progressive Massive Fibrosis; Complicated Silicosis

Outcome Measures

Primary Outcomes (1)

• Metabolic pulmonary activity assessed by PET-CT Scan (18 FFDG)

  Metabolic pulmonary activity assessed by PET-CT Scan (18 FFDG) in patients treated with pirfenidone vs control patients. The variables will be analyzed in lung and mediastinum independently and the measurement of the metabolic response will be based on the standardized uptake value (SUV) at its maximum (SUVmax) and mean (SUVmean) values.

  baseline (day 1), month 6, month 12

Secondary Outcomes (5)

• Cell biomarkers in peripheral blood: - Pro/anti fibrotic and pro/anti inflammatory biomarkers

  baseline (day 1), month 3, month 6, month 9, month 12

• Number of adverse events (AE) and adverse reactions (AR), of serious adverse events (SAE) and serious and unexpected adverse reactions (SUSAR).

  baseline (day 1), month 3, month 6, month 9, month 12

• Respiratory symptoms (cough, expectoration and dyspnea) and quality of life related to health using the EQ-5D 5L test.

  baseline (day 1), month 3, month 6, month 9, month 12

• Respiratory function variables

  baseline (day 1), month 3, month 6, month 9 and month 12

• Radiological categorization by chest radiology and by High Resolution Computed Tomography, following the International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases (ICOERD)

  baseline (day 1), month 6, month 12

Study Arms (2)

No intervention - standard of care

NO INTERVENTION

A group of patients with PMF will be treated per standard of care on site

Experimental - Pirfenidone plus standard of care

EXPERIMENTAL

A group of patients with PMF will be treated with pirfenidone plus standard of care on site

Drug: Pirfenidone Oral Tablet

Interventions

Pirfenidone Oral Tablet DRUG

Patients will be treated with pirfenidone (oral tablets) during 6 months

Also known as: Esbriet

Experimental - Pirfenidone plus standard of care

Eligibility Criteria

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

You may qualify if:

• \. Age over 18 years and under 65.
• \. Man with a diagnosis of silicosis in the form of PMF by lung or lymph node biopsy, or by radiological criteria.
• \. History of exposure to silica in work with artificial stone for at least 5 years.
• \. Patients capable of consenting to their participation in the study by providing written informed consent, or, if they are not trained, through a legal repressentative.

You may not qualify if:

• \. Participation in another clinical trial in the 6 months prior to the start of participation in this study.
• \. Hypersensitivity to any of the components of pirfenidone.
• \. Biological or farmacological treatment for any other disease or condition related to silicosis or PMF. Exception: prednisona (or equivalent) dose 20mg per day or lower.
• \. Concomitant treatment with a drug that can causes pirfenidone interactions: Cytotoxic drugs, immunosuppressants, cytokine modulators including but not limited to azathioprine, bosentan, ambrisentan, cyclophosphramide, cyclosporine, etarnecept, iloprost, infliximab, leukotriene antagonists, methotrexate, mycophenolate , tacrolimus, montelukast, tetrathiomolybdate, TNF-alpha inhibitors, imatinib mesylate, interferon gamma 1-beta, and tyrosine kinase inhibitors. Strong CYP1A2 inhibitors (eg fluvoxamine, enoxacin), P-glycoprotein or CYP3A4 inhibitors (eg Ketoconazole, erythromycin), or their inducers (eg rifampicin, carbamazepine, phenytoin). Other moderate CYP1A2 inhibitors (eg amiodarone or propafenone) which will also be prohibited. Any investigational therapy in an active clinical trial. Grapefruit juice.
• \. Active infectious disease.
• \. Any pathology that may condition the evolution of respiratory diseases, including cancer, HIV, HBV, HCV, liver cirrhosis, liver failure, severe kidney failure or any other that in the opinion of the investigator may interfere with the results of the study.
• \. Active smoking.
• \. Laboratory test abnormalities at screening timepoint - Total bilirrubin \>2 ULN - AST/SGOT or ALT/SGPT \> 2.5 ULN - Alkaline phosphatase \>3.0 ULN - Creatinine clearance \<40 mL/min (Cockcroft-Gault).
• \. Concomitant treatments that may cause serious digestive events.
• \. Digestive surgery or similar procedures that may cause digestive intolerances.
• \. Not availability to complete all the trial visits.
• \. Angiodema

Sponsors & Collaborators

• Instituto de investigación e innovación biomédica de Cádiz: lead

Study Sites (1)

Antonio León Jiménez

Cadiz, 11009, Spain

RECRUITING

MeSH Terms

Conditions

Silicosis

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Pneumoconiosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Occupational Diseases

Study Officials

• Antonio León Jiménez, MD

  Fundación Cádiz- INIBICA

  PRINCIPAL INVESTIGATOR

• Antonio Campos Caro, phD

  Fundación Cádiz- INIBICA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Quintana, phD

CONTACT

+34 639390856; laura.quintana@inibica.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Although this is an open study for participants and clinicians, professionals in charge of molecular and cellular analysis, HRCT and PET will be blind to the arm that each subject is assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: November 11, 2021
• Study Start: November 15, 2021
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2023
• Last Updated: January 13, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)