Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points
Background: Progressive pulmonary fibrosis (PPF) affects a group of patients with various underlying interstitial lung diseases (ILDs) who develop progressive fibrosis and exhibit a similar disease course to patients with idiopathic pulmonary fibrosis (IPF). In PPF, fibrosis becomes self-sustaining...
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Elsevier
2025-06-01
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| Series: | CHEST Pulmonary |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949789224000904 |
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| author | Steven D. Nathan, MD Juergen Behr, MD Vincent Cottin, MD Lisa Lancaster, MD Peter Smith, PharmD CQ Deng, PhD Natalie Breytenbach, PharmD Heidi Bell, MD Leigh Peterson, PhD Kevin R. Flaherty, MD |
| author_facet | Steven D. Nathan, MD Juergen Behr, MD Vincent Cottin, MD Lisa Lancaster, MD Peter Smith, PharmD CQ Deng, PhD Natalie Breytenbach, PharmD Heidi Bell, MD Leigh Peterson, PhD Kevin R. Flaherty, MD |
| author_sort | Steven D. Nathan, MD |
| collection | DOAJ |
| description | Background: Progressive pulmonary fibrosis (PPF) affects a group of patients with various underlying interstitial lung diseases (ILDs) who develop progressive fibrosis and exhibit a similar disease course to patients with idiopathic pulmonary fibrosis (IPF). In PPF, fibrosis becomes self-sustaining and behaves similarly across ILDs, irrespective of the initial trigger, with patients developing worsening respiratory symptoms, lung function, and quality of life and increased mortality despite usual treatments for the underlying ILD. Inhaled treprostinil has demonstrated improvements in FVC and reduced exacerbations of underlying lung disease in patients with pulmonary hypertension associated with ILD in post hoc analyses of a phase 3 study (Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE [INCREASE]) and its open-label extension. These results and preclinical evidence of treprostinil’s antifibrotic activity support its investigation in the treatment of PPF. Inhaled treprostinil is also being investigated for the treatment of IPF in the Study of Efficacy and Safety of Inhaled Treprostinil in Subjects with Idiopathic Pulmonary Fibrosis (TETON) and the Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2). Research Question: Does inhaled treprostinil improve absolute FVC over 52 weeks in patients with PPF? Study Design and Methods: The Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF) is a 52-week, randomized, double-blind, placebo-controlled, phase 3 study enrolling 698 patients. Eligible patients must have a diagnosis of PPF (other than IPF) with radiographic fibrosis of > 10% extent and FVC ≥ 45%. Background use of pirfenidone or nintedanib is allowed. The primary end point is change in absolute FVC at week 52. Secondary end points include time to first clinical worsening, time to first acute exacerbation of ILD, overall survival, change in % predicted FVC, change in the King’s Brief Interstitial Lung Disease Questionnaire, and change in lung diffusion capacity. Safety parameters include adverse events, hospitalizations, oxygenation, and laboratory parameters. Results: The study was initiated in October 2023 and will continue until 698 patients enroll. Interpretation: When completed, TETON-PPF will confirm whether inhaled treprostinil is safe and effective for the treatment of PPF. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT05943535; URL: www.clinicaltrials.gov |
| format | Article |
| id | doaj-art-fdbe313b92c44af7beee0f77c890bfc4 |
| institution | DOAJ |
| issn | 2949-7892 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | CHEST Pulmonary |
| spelling | doaj-art-fdbe313b92c44af7beee0f77c890bfc42025-08-20T02:55:19ZengElsevierCHEST Pulmonary2949-78922025-06-013210012410.1016/j.chpulm.2024.100124Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home PointsSteven D. Nathan, MD0Juergen Behr, MD1Vincent Cottin, MD2Lisa Lancaster, MD3Peter Smith, PharmD4CQ Deng, PhD5Natalie Breytenbach, PharmD6Heidi Bell, MD7Leigh Peterson, PhD8Kevin R. Flaherty, MD9Inova Fairfax Hospital, Falls Church, VA; CORRESPONDENCE TO: Steven D. Nathan, MDDepartment of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, GermanyCoordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Claude Bernard University Lyon, INRAE, member of ERN-LUNG, Lyon, FranceVanderbilt University Medical Center, Nashville, TNUnited Therapeutics Corp, Research Triangle Park, NCUnited Therapeutics Corp, Research Triangle Park, NCUnited Therapeutics Corp, Research Triangle Park, NCUnited Therapeutics Corp, Research Triangle Park, NCUnited Therapeutics Corp, Research Triangle Park, NCUniversity of Michigan, Ann Arbor, MIBackground: Progressive pulmonary fibrosis (PPF) affects a group of patients with various underlying interstitial lung diseases (ILDs) who develop progressive fibrosis and exhibit a similar disease course to patients with idiopathic pulmonary fibrosis (IPF). In PPF, fibrosis becomes self-sustaining and behaves similarly across ILDs, irrespective of the initial trigger, with patients developing worsening respiratory symptoms, lung function, and quality of life and increased mortality despite usual treatments for the underlying ILD. Inhaled treprostinil has demonstrated improvements in FVC and reduced exacerbations of underlying lung disease in patients with pulmonary hypertension associated with ILD in post hoc analyses of a phase 3 study (Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE [INCREASE]) and its open-label extension. These results and preclinical evidence of treprostinil’s antifibrotic activity support its investigation in the treatment of PPF. Inhaled treprostinil is also being investigated for the treatment of IPF in the Study of Efficacy and Safety of Inhaled Treprostinil in Subjects with Idiopathic Pulmonary Fibrosis (TETON) and the Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2). Research Question: Does inhaled treprostinil improve absolute FVC over 52 weeks in patients with PPF? Study Design and Methods: The Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF) is a 52-week, randomized, double-blind, placebo-controlled, phase 3 study enrolling 698 patients. Eligible patients must have a diagnosis of PPF (other than IPF) with radiographic fibrosis of > 10% extent and FVC ≥ 45%. Background use of pirfenidone or nintedanib is allowed. The primary end point is change in absolute FVC at week 52. Secondary end points include time to first clinical worsening, time to first acute exacerbation of ILD, overall survival, change in % predicted FVC, change in the King’s Brief Interstitial Lung Disease Questionnaire, and change in lung diffusion capacity. Safety parameters include adverse events, hospitalizations, oxygenation, and laboratory parameters. Results: The study was initiated in October 2023 and will continue until 698 patients enroll. Interpretation: When completed, TETON-PPF will confirm whether inhaled treprostinil is safe and effective for the treatment of PPF. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT05943535; URL: www.clinicaltrials.govhttp://www.sciencedirect.com/science/article/pii/S2949789224000904clinical trialinterstitial lung diseasephase 3progressive pulmonary fibrosis |
| spellingShingle | Steven D. Nathan, MD Juergen Behr, MD Vincent Cottin, MD Lisa Lancaster, MD Peter Smith, PharmD CQ Deng, PhD Natalie Breytenbach, PharmD Heidi Bell, MD Leigh Peterson, PhD Kevin R. Flaherty, MD Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points CHEST Pulmonary clinical trial interstitial lung disease phase 3 progressive pulmonary fibrosis |
| title | Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points |
| title_full | Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points |
| title_fullStr | Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points |
| title_full_unstemmed | Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points |
| title_short | Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary FibrosisTake-Home Points |
| title_sort | study design and rationale for the teton ppf phase 3 randomized controlled clinical trial of inhaled treprostinil in the treatment of progressive pulmonary fibrosistake home points |
| topic | clinical trial interstitial lung disease phase 3 progressive pulmonary fibrosis |
| url | http://www.sciencedirect.com/science/article/pii/S2949789224000904 |
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