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

NCTNCT07165028Other id27610Other id2025-522674-36-00Other idN1T-MC-MALOOther idN1T-MC-TZ01

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Overview

Status: Recruiting
Phase: Phase 3
Enrollment: 4,500 participants (estimated)
Sponsor: Eli Lilly and Company · Industry
Design: Randomized · Single masking
Countries: 30 countries
United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, South Korea, Spain, Sweden, Switzerland
Start: 15 Oct 2025
Primary completion: Aug 2030 (estimated)
Completion: Aug 2032 (estimated)
First posted: 10 Sept 2025
Last update posted: 8 Oct 2026
Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease

Timeline

1 trial · 1 ongoing

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2026202820302032

Ph 3
A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)
NCT07165028
15 Oct 2025 to est. Aug 2032

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

TirzepatideDrug
RetatrutideDrug
PlaceboDrug

Arms4

Experimental
Tirzepatide (TZ01)
Participants will receive tirzepatide subcutaneously (SC)
Placebo comparator
Placebo (TZ01)
Participants will receive placebo SC
Experimental
Retatrutide (RT01)
Participants will receive retatrutide SC
Placebo comparator
Placebo (RT01)
Participants will receive placebo SC

Primary outcomes1

Outcomes the sponsor listed as primary.

Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
Time frame · Baseline up to Study Completion (about 224 weeks)
Registry description
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

Secondary outcomes(9)

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)
Time frame · Baseline up to Study Completion (about 224 weeks)
Registry description
MACE-3 composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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