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

NCT07165028
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Recruiting
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Participants
4,500
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Lead sponsor
Eli Lilly and Company
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Start date
2025-10-15
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Number of sites
565
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Summary
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.
clinicaltrials.gov
Short title
A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)
clinicaltrials.gov
Official title
A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2032-08-01
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First posted
2025-09-10
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Registry last updated
2026-08-21
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Primary completion date
2030-08-01
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Start date
2025-10-15
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Participants
4,500
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Participant count basis
Estimated
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Planned participants
4,500
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Protocol amendments
0
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Number of sites
565
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07165028
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ClinicalTrials.gov ID
NCT07165028
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Single masking
Masked roles
Participants
Sources for study design
clinicaltrials.gov

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

    Timeframe: Baseline up to Study Completion (about 224 weeks)

    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

  1. Change from Baseline in Enhanced Liver Fibrosis (ELF) Score

    Timeframe: Baseline, Week 104

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

    Timeframe: Baseline, Week 104

  3. Percent Change from Baseline in Liver Fat Content (LFC)

    Timeframe: Baseline, Week 104

  4. Time to Occurrence of Progression to Cirrhosis

    Timeframe: Baseline up to Study Completion (about 224 weeks)

  5. Change from Baseline in Aspartate Aminotransferase (AST)

    Timeframe: Baseline, Study Completion (about 224 weeks)

  6. Change from Baseline in Alanine Aminotransferase (ALT)

    Timeframe: Baseline, Study Completion (about 224 weeks)

  7. Change from Baseline in Body Weight

    Timeframe: Baseline, Study Completion (about 224 weeks)

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

    Timeframe: Baseline, Week 104

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

    Timeframe: Baseline up to Study Completion (about 224 weeks)

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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
clinicaltrials.gov

  • MFA Clinical ResearchTuscaloosa, United StatesRecruiting
  • The Institute for Liver Health II dba Arizona Clinical Trials - ChandlerChandler, United StatesRecruiting
  • Spectrum Research InstituteGilbert, United StatesRecruiting
  • The Institute for Liver Health II dba Arizona Liver Health - PeoriaPeoria, United StatesRecruiting
  • Epic Medical Research-Sun CitySun City, United StatesRecruiting
  • The Institute for Liver Health II dba Arizona Clinical Trials - TucsonTucson, United StatesRecruiting
  • Del Sol Research Management, LLCTucson, United StatesRecruiting
  • Arkansas Gastroenterology - North Little RockNorth Little Rock, United StatesRecruiting
  • San Fernando Valley Health InstituteCanoga Park, United StatesRecruiting
  • Ark Clinical Research - Fountain ValleyFountain Valley, United StatesRecruiting
  • Fresno Clinical Research CenterFresno, United StatesRecruiting
  • UCSD - Altman Clinical and Translational Research Institute (ACTRI)La Jolla, United StatesRecruiting
  • Orange County Research CenterLake Forest, United StatesRecruiting
  • Om Research LLCLancaster, United StatesRecruiting
  • Ark Clinical ResearchLong Beach, United StatesRecruiting
  • Los Angeles Institute for Metabolic ResearchLos Angeles, United StatesRecruiting
  • United Medical Doctors - MurrietaMurrieta, United StatesRecruiting
  • Knowledge Research CenterOrange, United StatesRecruiting
  • California Liver Research CenterPasadena, United StatesRecruiting
  • Artemis Institute for Clinical ResearchRiverside, United StatesRecruiting
  • Medical Associates Research GroupSan Diego, United StatesRecruiting
  • Quest Clinical ResearchSan Francisco, United StatesRecruiting
  • University of Colorado Anschutz Medical CampusAurora, United StatesRecruiting
  • South Denver GastroenterologyEnglewood, United StatesRecruiting
  • Medical Research Center of ConnecticutHamden, United StatesRecruiting

And 540 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-522674-36-00
  • N1T-MC-MALO
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (1)

Targets (3)