Author information
1Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London and King's College Hospital, London, UK.
2College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
3VCU School of Medicine, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Richmond, Virginia, USA.
4Novo Nordisk A/S, Copenhagen, Denmark.
5Department of Medical Sciences, University of Turin, Turin, Italy.
6Division of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois, USA.
7Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
8Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
9German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.
10Sorbonne Université, Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France.
Abstract
Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction-associated steatohepatitis (MASH).
Aims: To describe the trial design and baseline characteristics of the 'Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis' (ESSENCE) trial (NCT04822181).
Methods: ESSENCE is a two-part, phase 3, randomised, multicentre trial evaluating the effect of subcutaneous semaglutide 2.4 mg in participants with biopsy-proven MASH and fibrosis stage 2 or 3. The primary objective of Part 1 is to demonstrate that semaglutide improves liver histology compared with placebo. The two primary endpoints are: resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. The Part 2 objective is based on clinical outcomes. The current work reports baseline characteristics of the first 800 randomised participants which includes demographics, laboratory parameters, liver histology, non-invasive tests and presence of metabolic dysfunction-associated steatotic liver disease (MASLD) cardiometabolic criteria.
Results: Of 800 participants, 250 (31.3%) had fibrosis stage 2 and 550 (68.8%) had fibrosis stage 3. In the overall population, mean (standard deviation [SD]) age was 56 (11.6) years, 57.1% were female, mean (SD) body mass index was 34.6 (7.2) kg/m2, 55.5% had type 2 diabetes and > 99% had at least one MASLD cardiometabolic criterion according to the published definition.
Conclusion: The ESSENCE baseline population includes participants with clinically significant fibrosis stages 2 and 3. Although MASLD cardiometabolic criteria were not a requirement for study enrolment, almost all participants (> 99%) had at least one MASLD cardiometabolic criterion.
Trial registration: NCT04822181.