Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis

  • Chest. 2018 Nov;154(5):1061-1069. doi: 10.1016/j.chest.2018.08.1058.
Scott M Palmer  1 ,  Laurie Snyder  2 ,  Jamie L Todd  2 ,  Benjamin Soule  3 ,  Rose Christian  3 ,  Kevin Anstrom  4 ,  Yi Luo  3 ,  Robert Gagnon  3 ,  Glenn Rosen  3
Affiliations
  • 1. Division of Pulmonary and Critical Care Medicine, Duke University, Durham, NC; Duke Clinical Research Institute, Durham, NC. Electronic address: [email protected].
  • 2. Division of Pulmonary and Critical Care Medicine, Duke University, Durham, NC; Duke Clinical Research Institute, Durham, NC.
  • 3. Bristol-Myers Squibb, Princeton, NJ.
  • 4. Duke Clinical Research Institute, Durham, NC.
PMID: 30201408 DOI: 10.1016/j.chest.2018.08.1058
Abstract

Background: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. The lysophosphatidic acid receptor 1 (LPA1) pathway is implicated in IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA1 antagonist, was assessed vs placebo in a phase 2 study in patients with IPF.

Methods: IM136003 was a phase 2, parallel-arm, multicenter, randomized, double-blind, placebo-controlled trial. Adults with IPF (FVC, 45%-90%; diffusing capacity for carbon monoxide, 30%-80%) were randomized to receive placebo or 600 mg BMS-986020 (once daily [qd] or bid) for 26 weeks. The primary end point was rate of change in FVC from baseline to week 26.

Results: Of 143 randomized patients, 108 completed the 26-week dosing phase. Thirty-five patients discontinued prematurely. Patient baseline characteristics were similar between treatment groups (placebo: n = 47; 600 mg qd: n = 48; 600 mg bid: n = 48). Patients treated with BMS-986020 bid experienced a significantly slower rate of decline in FVC vs placebo (-0.042 L; 95% CI, -0.106 to -0.022 vs -0.134 L; 95% CI, -0.201 to -0.068, respectively; P = .049). Dose-related elevations in hepatic Enzymes were observed in both BMS-986020 treatment groups. The study was terminated early because of three cases of cholecystitis that were determined to be related to BMS-986020 after unblinding.

Conclusions: BMS-986020 600 mg bid treatment for 26 weeks vs placebo significantly slowed the rate of FVC decline. Both regimens of BMS-986020 were associated with elevations in hepatic Enzymes.

Trial registry: ClinicalTrials.gov; No.: NCT01766817; URL: www.clinicaltrials.gov.

Keywords
clinical trial; idiopathic pulmonary fibrosis; lysophosphatidic acid receptor antagonist.
Products