Randomised clinical trial: Design of the SYNERGY-NASH phase 2b trial to evaluate tirzepatide as a treatment for metabolic dysfunction-associated steatohepatitis and modification of screening strategy to reduce screen failures.

Autor: Vuppalanchi R; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Loomba R; MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA., Sanyal AJ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA., Nikooie A; Eli Lilly and Company, Indianapolis, Indiana, USA., Tang Y; Eli Lilly and Company, Indianapolis, Indiana, USA., Robins DA; Eli Lilly and Company, Indianapolis, Indiana, USA., Brouwers B; Eli Lilly and Company, Indianapolis, Indiana, USA., Hartman ML; Eli Lilly and Company, Indianapolis, Indiana, USA.
Jazyk: angličtina
Zdroj: Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2024 Jul; Vol. 60 (1), pp. 17-32. Date of Electronic Publication: 2024 May 20.
DOI: 10.1111/apt.18042
Abstrakt: Background: The use of histological inclusion criteria for clinical trials of at-risk metabolic dysfunction-associated steatohepatitis (MASH) is often associated with high screen failure rates.
Aims: To describe the design of a trial investigating tirzepatide treatment of MASH and to examine the effect of new inclusion criteria incorporating the use of the FibroScan-AST (FAST) score on the proportion of patients meeting histological criteria.
Methods: SYNERGY-NASH is a Phase 2b, multicentre, randomised, double-blinded, placebo-controlled trial in patients with biopsy-confirmed MASH, F2-F3 fibrosis and NAFLD Activity Score ≥4. New inclusion criteria (FAST score >0.35 and an increase in AST inclusion criterion from >20 to >23 U/L) were adopted during the trial, allowing us to examine its impact on the qualification rate.
Results: 1583 participants were screened, 651 participants proceeded to liver biopsy and 190 participants were randomised with an overall screen fail rate of 87%. Following the protocol amendment, the overall qualification rate for per-protocol biopsies was minimally changed from 27.5% to 28.9% with considerable variation among different investigator medical speciality types: endocrinology: from 37.5% to 39.3%; gastroenterology/hepatology: from 26.0% to 23.3%; other specialities: from 21.3% to 29.7%. At 29 sites that performed per-protocol biopsies before and after the amendment, qualification rates changed as follows: all: 26.1% to 29.1%; endocrinology: from 35.0% to 40.9%; gastroenterology/hepatology: 25.6% to 20.0%; other specialities: from 16.1% to 27.8%.
Conclusions: For at-risk MASH trials based on liver histology, the implementation of inclusion criteria with the proposed FAST score and AST cut-offs in this trial was most effective at non-specialist sites.
(© 2024 Eli Lilly and Company and The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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