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

Philip N. Newsome (), Arun J. Sanyal, Guy Neff, Jörn M. Schattenberg, Vlad Ratziu, Judith Ertle, Jasmin Link, Alison Mackie, Corinna Schoelch and Eric Lawitz
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Philip N. Newsome: Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust
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

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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 (

Date: 2023
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DOI: 10.1038/s41467-023-42398-w

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