A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)

Phase 3RecruitingNCT07165028

Eli Lilly and Company4,500 enrolled

Overview

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression. Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

4,500

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have liver fat content ≥8% * Have ELF score of ≥9 and ≤10.8 at screening * Have VCTE LSM ≥10 kilopascal (kPa) and \<20 kPa at screening Exclusion Criteria: * Have any other type of liver disease other than MASLD * Have a body mass index (BMI) \<25 kilogram per square meter (kg/m2) * Prior decompensated liver disease (history of esophageal/gastric varices, ascites, hepatic encephalopathy) * Have lost more than 11 pounds within the 3 months prior to screening * Have a hemoglobin A1c (HbA1c) greater than 10% * Have type 1 diabetes

Locations (557)

MFA Clinical Research

Tuscaloosa, Alabama, United States

NOT_YET_RECRUITING

The Institute for Liver Health II dba Arizona Clinical Trials - Chandler

Chandler, Arizona, United States

RECRUITING

Spectrum Research Institute

Gilbert, Arizona, United States

RECRUITING

The Institute for Liver Health II dba Arizona Liver Health - Peoria

Peoria, Arizona, United States

Outcomes

Primary Outcomes

Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)

Composite endpoint comprised of progression to cirrhosis, development of large esophageal varices, gastric varices or development of varices needing treatment, development of ascites, development of hepatic encephalopathy, evidence of active or recent variceal hemorrhage, increase in model for end-stage liver disease (MELD) from ≤12 to ≥15, liver transplantation, all-cause mortality

Time frame: Baseline up to Study Completion (about 224 weeks)

Secondary Outcomes

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score

Time frame: Baseline, Week 104

Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)

Time frame: Baseline, Week 104

Percent Change from Baseline in Liver Fat Content (LFC)

Time frame: Baseline, Week 104

Time to Occurrence of Progression to Cirrhosis

Time frame: Baseline up to Study Completion (about 224 weeks)

Change from Baseline in Aspartate Aminotransferase (AST)

Time frame: Baseline, Study Completion (about 224 weeks)

Change from Baseline in Alanine Aminotransferase (ALT)

Time frame: Baseline, Study Completion (about 224 weeks)

Change from Baseline in Body Weight

Time frame: Baseline, Study Completion (about 224 weeks)

Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)

Time frame: Baseline, Week 104

Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)

MACE-3 composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death

Time frame: Baseline up to Study Completion (about 224 weeks)

Central Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559 LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com