Health Trials

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

ConditionMetabolic Dysfunction-Associated Steatotic Liver Disease
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorEli Lilly and Company

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Tirzepatide

    Drug

    Administered SC

  • Retatrutide

    Drug

    Administered SC

  • Placebo

    Drug

    Administered SC

Treatment groups

4,500 Participants
are divided into 4 treatment groups
Group A: Tirzepatide (TZ01)Experimental treatment 1 intervention
Group B: Placebo (TZ01)Placebo comparator 1 intervention
Group C: Retatrutide (RT01)Experimental treatment 1 intervention
Group D: Placebo (RT01)Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

1

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score

Time frame
Baseline, Week 104
2

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

Time frame
Baseline, Week 104
3

Percent Change from Baseline in Liver Fat Content (LFC)

Time frame
Baseline, Week 104
4

Time to Occurrence of Progression to Cirrhosis

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

Other outcomes

Sponsors and contacts

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Eli Lilly and Company

Lead sponsor

Source ClinicalTrials.gov
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