Dual αvβ6 and αvβ1 Inhibition Over 12 Weeks Reduces Active Type 1 Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial.

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of type 1 collagen. Ga-CBP8, a type 1 collagen positron emission tomography (PET) 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 αβ and αβ integrins under late-stage evaluation for treatment of IPF. Evaluate changes in type 1 collagen in the lungs of participants with IPF following treatment with bexotegrast. In this Phase 2 (NCT05621252), single-center, double-blind, placebo-controlled study, adults with IPF received bexotegrast 160mg or placebo for 12 weeks. Primary endpoint was the change in whole-lung standardized uptake value (SUV) of Ga-CBP8 PET. Changes in lung dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters, forced vital capacity (FVC), cough severity, and biomarkers of collagen synthesis and progressive disease were also assessed. Of 10 participants, 7 received bexotegrast and 3 placebo. At Week 12, mean change from baseline in top quartile of Ga-CBP8 whole-lung SUV was -1.2% with bexotegrast vs 6.6% with placebo; greatest mean changes were observed in subpleural lung regions in both groups (bexotegrast, -3.7%; placebo, 10.3%). DCE-MRI demonstrated 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 biomarker levels. The reduced uptake of Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling.