Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • J. Stuart Elborn
  • Michael W. Konstan
  • Jennifer L. Taylor-cousar
  • Isabelle Fajac
  • Sivagurunathan Sutharsan
  • Shawn D. Aaron
  • Cori L. Daines
  • Ahmet Uluer
  • Damian G. Downey
  • Vincenzina V. Lucidi
  • Sanjeev Ahuja
  • Eric Springman
  • John Mershon
  • Ralph Grosswald
  • Steven M. Rowe


Background Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB4) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB4 production. We report findings from a randomized placebo-controlled trial of acebilustat in adult subjects with mild-to-moderate lung disease. Methods Subjects were randomized (1:1:1) to once-daily acebilustat 50 mg, 100 mg or placebo for 48 weeks, concomitantly with their current therapeutic regimen. Subjects were stratified by use of concomitant CF transmembrane conductance regulator (CFTR) modulators, baseline percent predicted forced expiratory volume in 1 second (ppFEV1) 50-75 and >75, and number of pulmonary exacerbations in the past year (1 or >1). Primary endpoints were the change from baseline in ppFEV1 and safety. Secondary endpoints included the rate of pulmonary exacerbations. Results Overall, 199 subjects were randomized and dosed (acebilustat 50 mg, n=67; acebilustat 100 mg, n=66; placebo, n=66). Baseline demographics and disease profile were well balanced among treatment groups. Acebilustat had no statistically significant effect on the primary endpoint of change in ppFEV1 at week 48 or the secondary endpoint pulmonary exacerbations. There was a trend towards reduced pulmonary exacerbations in subjects receiving acebilustat in pre-specified populations with ppFEV1>75 (35% rate reduction) and those on concomitant CFTR modulator therapy (20% rate reduction). Acebilustat was well tolerated. Conclusions Acebilustat did not improve lung function. A trend towards reduced pulmonary exacerbations in subjects with an earlier stage of lung disease suggests a potential effect in this population.

Bibliographical metadata

Original languageEnglish
JournalJournal of Cystic Fibrosis
Early online date17 Sep 2021
Publication statusPublished - 17 Sep 2021