Study Design and Rationale for the TETON-PPF Phase 3, Randomized, Controlled Clinical Trial of Inhaled Treprostinil in the Treatment of Progressive Pulmonary Fibrosis

• Published in: CHEST pulmonary 2024-11, p.100124, Article 100124
• Main Authors: Nathan, Steven D., Behr, Juergen, Cottin, Vincent, Lancaster, Lisa, Smith, Peter, Deng, C.Q., Breytenbach, Natalie, Bell, Heidi, Peterson, Leigh, Flaherty, Kevin R.
• Format: Article
• Language: English
• Subjects: Clinical Trial; Interstitial Lung Disease; Phase 3; Progressive Pulmonary fibrosis
• ISSN: 2949-7892; 2949-7892
• DOI: 10.1016/j.chpulm.2024.100124

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 idiopathic pulmonary fibrosis (IPF) patients. In PPF, fibrosis becomes self-sustaining and behaves similarly across ILDs, irrespective of the initial trigger, with patients developing worsening respiratory symptoms, lung function, quality of life, and increased mortality despite usual treatments for the underlying ILD. Inhaled treprostinil demonstrated improvements in forced vital capacity (FVC) and reduced exacerbations of underlying lung disease in patients with pulmonary hypertension associated with interstitial lung disease in post-hoc analyses of a Phase 3 study (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 TETON studies (RIN-PF-301, NCT04708782; RIN-PF-303, NCT05255991). Does inhaled treprostinil improve absolute FVC over 52 weeks in patients with PPF? 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 endpoint is change in absolute FVC at Week 52. Secondary endpoints 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. The study was initiated in October 2023 and will continue until 698 patients enroll. When completed, TETON-PPF will confirm whether inhaled treprostinil is safe and effective for the treatment of PPF.