Dual αvβ6 and αvβ1 Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial
Sydney B. Montesi, Gregory P. Cosgrove, Scott Turner, Iris Y. Zhou, Nikos Efthimiou, Antonia Šušnjar, Ciprian Catana, Caroline Fromson, Annie Clark, Martin Decaris, Chris N. Barnes, Éric Lefebvre, Peter Caravan
Abstract
Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of type I collagen. 68Ga-CBP8, a type I collagen positron emission tomography probe, measures collagen accumulation and shows higher collagen deposition in patients with IPF. Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of αvβ6 and αvβ1 integrins under late-stage evaluation for treatment of IPF. Objectives To evaluate changes in type I collagen in the lungs of participants with IPF after treatment with bexotegrast. Methods In this phase 2 (NCT05621252), single-center, double-blind, placebo-controlled study, adults with IPF received bexotegrast 160 mg or placebo for 12 weeks. The primary endpoint was the change in whole-lung standardized uptake value of 68Ga-CBP8 positron emission tomography. Changes in lung dynamic contrast-enhanced magnetic resonance imaging parameters, FVC, cough severity, and biomarkers of collagen synthesis and progressive disease were also assessed. Measurements and Main Results Of 10 participants, 7 received bexotegrast and 3 received placebo. At Week 12, the mean change from baseline in the top quartile of 68Ga-CBP8 whole-lung standardized uptake value was −1.2% with bexotegrast versus 6.6% with placebo; the greatest mean changes were observed in subpleural lung regions in both groups (bexotegrast, −3.7%; placebo, 10.3%). Dynamic contrast-enhanced magnetic resonance imaging showed numerically increased peak enhancement and faster contrast washout rate in bexotegrast-treated participants, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume. Bexotegrast treatment resulted in numerical improvements in FVC, cough severity, and biomarkers. Conclusions The reduced uptake of 68Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling.