Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study

Abstract

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, randomized, double-blind, placebo-controlled dose-escalation study, 24 participants with IPF were randomized 3:1 to inhaled LTI-03 5 mg/day (N = 9), LTI-03 10 mg/day (N = 9) or placebo (N = 6) for 14 days and included in all analyses (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and disease-related biomarkers. LTI-03 was well-tolerated, with no treatment-related discontinuations, no severe TEAEs, and no evidence of airway obstruction by spirometry and associated symptoms. In deep bronchial brushings, both LTI-03 doses significantly reduced interleukin-11 (p = 0.0406 at 5 mg/day; p = 0.044 at 10 mg/day) and thymic stromal lymphopoietin (p = 0.0256 at 5 mg/day; p = 0.0128 at 10 mg/day) versus placebo. The 10 mg/day dose suppressed collagen type 1 alpha chain 1 (p = 0.0248), CXC chemokine ligand 7 (p = 0.0248) and galectin-7 (p = 0.0332). Other measured biomarkers were not significantly changed. The favorable safety profile and reductions in disease-related biomarkers support further evaluation of inhaled LTI-03 for IPF. This study was fully funded by Rein Therapeutics, Inc.