GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial
Irina Strâmbu, Christian A. Seemayer, Liesbeth Fagard, Paul A. Ford, Tom A.K. Van der Aa, Angela A. de Haas-Amatsaleh, Vikas Modgill, Eva Santermans, Eric Sondag, Eric Helmer, Toby M. Maher, Ulrich Costabel, Vincent Cottin
Abstract
Background GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF). Methods PINTA ( ClinicalTrials.gov : NCT03725852 ) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance. Results In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was −33.68 (95% CI −112.0–44.68) mL with GLPG1205 and −76.00 (95% CI −170.7–18.71) mL with placebo (least squares mean difference 42.33 (95% CI −81.84–166.5) mL; p=0.50). Lung volumes by imaging declined −58.30 versus −262.72 mL (whole lung) and −33.68 versus −135.48 mL (lower lobes) with GLPG1205 versus placebo, respectively. Treatment with GLPG1205 versus placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib. Conclusions Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.