SilicosisPhase 2NCT05118256
Pirfenidone for the Reduction of Metabolic, Inflammatory and Fibrogenic Activity in Complicated Silicosis
A Phase 2 study testing Pirfenidone Oral Tablet in people with Silicosis and Progressive Massive Fibrosis, run by Instituto de investigación e innovación biomédica de Cádiz at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Silicosis, Progressive Massive Fibrosis, Complicated Silicosis
- What is being tested?
- Pirfenidone Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSpain
- Study dates
- 15 Nov 2021to 15 Nov 2023
- 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Age over 18 years and under 65.
- 2. Man with a diagnosis of silicosis in the form of PMF by lung or lymph node biopsy, or by radiological criteria.
- 3. History of exposure to silica in work with artificial stone for at least 5 years.
- 4. 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.
Who cannot join
- 1. Participation in another clinical trial in the 6 months prior to the start of participation in this study.
- 2. Hypersensitivity to any of the components of pirfenidone.
- 3. 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.
- 4. 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.
- 5. Active infectious disease.
- 6. 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.
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- 7. Active smoking.
- 8. 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).
- 9. Concomitant treatments that may cause serious digestive events.
- 10. Digestive surgery or similar procedures that may cause digestive intolerances.
- 11. Not availability to complete all the trial visits.
- 12. Angiodema
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Antonio León Jiménez
Cadiz, 11009
Antonio León Jiménez, MD
About this study
Official title: An Open, Randomised, Controlled and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF
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).
Read the detailed description
Hypothesis: Pirfenidone reduces pulmonary metabolic activity in patients with Progressive Massive Fibrosis (PMF).
Objetives:
Main objetive: To evaluate the efficacy of pirfenidone in reducing pulmonary metabolic activity quantified by PET-CT Scan (F-FDG) in patients with Progressive Massive Fibrosis (PMF).
Secundary objetives:
- To evaluate the efficacy of pirfenidone in reducing pulmonary inflammatory and fibrogenic activity in patients with Progressive Massive Fibrosis (PMF), quantified by cell biomarkers, and the relation with the pulmonary metabolic activity.
- To assess changes brought about by pirfenidone in the different cells biomarkers patterns and metabolic activity resulted by PET/TC with 18-FDG
- To assess radiological changes in HRCT (High Resolution Computed Tomography) that occur after administration of pirfenidone and the relation with biomarkers and with 18F FDG acquisition.
- To assess wheter administration of pirfenidone generates changes on standard funtional respiratory explorations, and the relation with inflammatory and metabolic activity. 5. To assess clinical changes (if any) and safety of pirfenidone after administration to patients with PMF.
Methodology: An Open, Randomised, Controlled, 2 arms and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF.
- Being tested
- Pirfenidone Oral Tablet
- Medical subject headings
- Silicosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pirfenidone Oral TabletDrug
Also called Esbriet
Patients will be treated with pirfenidone (oral tablets) during 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pirfenidone Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline (day 1), month 6, month 12
Secondary outcomes (5)
Cell biomarkers in peripheral blood: - Pro/anti fibrotic and pro/anti inflammatory biomarkers
Pro/anti fibrotic and pro/anti inflammatory biomarkers: cytokines (IL-1α, IL-1β, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17, IL-18, IP-10, TGF-β, TNF-α, IFN-γ, MIP-1α, MIP-1β, MCP-1, PDGF, bFGF, MMP1, -2, -7, -9, -10). Immunological biomarkers: CD45, CD45RO, CD45RA, CD3, CD4, CD8, CD19, CD27, CD56, CD126, CD25, INF-γ, IL-4, FoxP3, CD196 y CD161 Note: There are no previous studies in patients with artificial stone silicosis in which they have analyzed the indicated biomarkers. This is a comprehensive preliminary analysis of biomarkers and we want to correlate the obtained values with the results derived from PET-CT in both groups of patients in the trial.
Measured: 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).
Number of adverse events (AE) and adverse reactions (AR), of serious adverse events (SAE) and serious and unexpected adverse reactions (SUSAR).
Measured: 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.
Respiratory symptoms (cough, expectoration and dyspnea) and quality of life related to health using the EQ-5D 5L test.
Measured: baseline (day 1), month 3, month 6, month 9, month 12
Respiratory function variables
Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second, ratio Forced Expiratory in the first second / Forced Vital Capacity and Diffusing Capacity of the lungs for carbon monoxide, obtained through standardized respiratory function tests.
Measured: 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)
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)
Measured: baseline (day 1), month 6, month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start15 Nov 2021
- Primary completion15 Nov 2022 (estimated)
- Study completion15 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SilicosisStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de investigación e innovación biomédica de Cádiz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio León Jiménez, MD, Principal investigator, Fundación Cádiz- INIBICAAntonio Campos Caro, phD, Principal investigator, Fundación Cádiz- INIBICA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118256
- Sponsor's protocol ID
- FUN-PIR-2020-01
- Status last verified
- Dec 2021
- First submitted
- 1 Oct 2021
- Last updated
- 13 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The study results will be published in scientific pneumologic journal and available in PubMed and clinicaltrials website
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Randomised, Controlled and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF
- ClinicalTrials.gov ID
- NCT05118256
- Acronym / sponsor ID
- FUN-PIR-2020-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Instituto de investigación e innovación biomédica de CádizUniversity, hospital or other
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- 15 Nov 2022 (estimated)
- Study completion
- 15 Nov 2023 (estimated)
- First posted
- 11 Nov 2021 (actual)
- 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.
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).
Detailed description
Hypothesis: Pirfenidone reduces pulmonary metabolic activity in patients with Progressive Massive Fibrosis (PMF).
Objetives:
Main objetive: To evaluate the efficacy of pirfenidone in reducing pulmonary metabolic activity quantified by PET-CT Scan (F-FDG) in patients with Progressive Massive Fibrosis (PMF).
Secundary objetives:
- To evaluate the efficacy of pirfenidone in reducing pulmonary inflammatory and fibrogenic activity in patients with Progressive Massive Fibrosis (PMF), quantified by cell biomarkers, and the relation with the pulmonary metabolic activity.
- To assess changes brought about by pirfenidone in the different cells biomarkers patterns and metabolic activity resulted by PET/TC with 18-FDG
- To assess radiological changes in HRCT (High Resolution Computed Tomography) that occur after administration of pirfenidone and the relation with biomarkers and with 18F FDG acquisition.
- To assess wheter administration of pirfenidone generates changes on standard funtional respiratory explorations, and the relation with inflammatory and metabolic activity. 5. To assess clinical changes (if any) and safety of pirfenidone after administration to patients with PMF.
Methodology: An Open, Randomised, Controlled, 2 arms and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Pirfenidone Oral TabletA group of patients with PMF will be treated with pirfenidone plus standard of care on site |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 1. Age over 18 years and under 65.
- 2. Man with a diagnosis of silicosis in the form of PMF by lung or lymph node biopsy, or by radiological criteria.
- 3. History of exposure to silica in work with artificial stone for at least 5 years.
- 4. 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.
Key exclusion criteria (12 listed)
- 1. Participation in another clinical trial in the 6 months prior to the start of participation in this study.
- 2. Hypersensitivity to any of the components of pirfenidone.
- 3. 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.
- 4. 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.
- 5. Active infectious disease.
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 |
|---|---|---|
| Pirfenidone Oral TabletAlso: EsbrietPatients will be treated with pirfenidone (oral tablets) during 6 months | Drug | Experimental - Pirfenidone plus standard of care |
Primary outcome
Metabolic pulmonary activity assessed by PET-CT Scan (18 FFDG)
Time frame: baseline (day 1), month 6, month 12
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.
5 secondary outcomes
Cell biomarkers in peripheral blood: - Pro/anti fibrotic and pro/anti inflammatory biomarkers
Time frame: 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).
Time frame: 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.
Time frame: baseline (day 1), month 3, month 6, month 9, month 12
Respiratory function variables
Time frame: 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)
Time frame: baseline (day 1), month 6, month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2022.
- Individual participant dataSharing planned: No. The study results will be published in scientific pneumologic journal and available in PubMed and clinicaltrials website
Related trials for Silicosis
Not yet recruitingObservational study
Perioperative Risk Factors Related to the Prognosis of Lung Transplantation: A Retrospective Study
COPD, Interstitial Pneumonia
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.
Antonio León Jiménez, MD principal investigator
Fundación Cádiz- INIBICA
Antonio Campos Caro, phD principal investigator
Fundación Cádiz- INIBICA
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 Pirfenidone Oral Tablet in people with Silicosis and Progressive Massive Fibrosis, run by Instituto de investigación e innovación biomédica de Cádiz at 1 site in Spain.
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 4 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 13 Jan 2022. 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 Spain. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laura Quintana, phD (+34 639390856, laura.quintana@inibica.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic pulmonary activity assessed by PET-CT Scan (18 FFDG) (time frame: baseline (day 1), month 6, month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2022.