Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis

study Investigators, Michael W. Konstan, Deepika Polineni, James F. Chmiel, Lara Bilodeau, Peter G. Middleton, Elias Matouk, Jean Marie Houle, Radu Pislariu, Patrick Colin, Irenej Kianicka, Diane Potvin, Danuta Radzioch, Tom Kotsimbos, Jonathan B. Zuckerman, Samya Z. Nasr, Theodore G. Liou, Larry C. Lands

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF. Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks. Results: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile. Conclusion: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.

Original languageEnglish
JournalJournal of Cystic Fibrosis
DOIs
StateAccepted/In press - 2024

Keywords

  • CFTR modulators
  • Cystic fibrosis
  • Inflammation
  • LAU-7b
  • Lung function loss reduction

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