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A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis

Author

Listed:
  • Philip N. Newsome

    (Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust
    University of Birmingham)

  • Arun J. Sanyal

    (Virginia Commonwealth University)

  • Guy Neff

    (Covenant Research)

  • Jörn M. Schattenberg

    (Metabolic Liver Research Program University Medical Center)

  • Vlad Ratziu

    (Sorbonne Université, Institute of Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière)

  • Judith Ertle

    (Boehringer Ingelheim)

  • Jasmin Link

    (Boehringer Ingelheim)

  • Alison Mackie

    (Boehringer Ingelheim)

  • Corinna Schoelch

    (Boehringer Ingelheim)

  • Eric Lawitz

    (University of Texas Health)

Abstract

Non-alcoholic steatohepatitis (NASH) is a progressive, inflammatory liver disease with no approved pharmacological treatment. This Phase IIa, double-blind, placebo-controlled, multicentre trial (ClinicalTrials.gov: NCT03166735) investigated pharmacodynamics and safety of BI 1467335, an amine oxidase copper-containing 3 (AOC3) inhibitor, in adults with NASH from Europe and North America. Participants from 44 centres across the US, Germany, Spain, Belgium, the UK, Netherlands, Canada, France and Ireland were randomised (2:1:1:1:2; 27 July 2017 to 14 June 2019) to daily oral BI 1467335 1 mg (n = 16), 3 mg (n = 16), 6 mg (n = 17), 10 mg (n = 32) or placebo (n = 32) for 12 weeks, with follow-up to Week 16. Primary endpoint was AOC3 activity relative to baseline (%), 24 hours post-dose after 12 weeks’ treatment. Secondary biomarker endpoints included changes from baseline at Week 12 in alanine aminotransferase (ALT) and caspase-cleaved cytokeratin 18 (CK-18 caspase). Mean AOC3 activities relative to baseline at Week 12: 90.4% (placebo; n = 32), 26.5% (1 mg; n = 16), 10.4% (3 mg; n = 16), 5.0% (6 mg; n = 16), 3.3% (10 mg; n = 32). These changes indicated that BI 1467335 dose-dependently inhibited AOC3 activity; ≥3 mg doses achieved >80% inhibition (

Suggested Citation

  • Philip N. Newsome & Arun J. Sanyal & Guy Neff & Jörn M. Schattenberg & Vlad Ratziu & Judith Ertle & Jasmin Link & Alison Mackie & Corinna Schoelch & Eric Lawitz, 2023. "A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42398-w
    DOI: 10.1038/s41467-023-42398-w
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    References listed on IDEAS

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    1. Bornkamp, Björn & Pinheiro, José & Bretz, Frank, 2009. "MCPMod: An R Package for the Design and Analysis of Dose-Finding Studies," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 29(i07).
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