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

Lilly

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease

Treatments: Drug: Tirzepatide; Drug: Placebo; Drug: Retatrutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT07165028

N1T-MC-MALO (Other Identifier)

N1T-MC-RT01 (Other Identifier)

27610

2025-522674-36-00 (EU Trial (CTIS) Number)

N1T-MC-TZ01 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 4,500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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4,500 participants in 4 patient groups, including a placebo group

Tirzepatide (TZ01)

Experimental group

Description:

Participants will receive tirzepatide subcutaneously (SC)

Treatment:

Drug: Tirzepatide

Placebo (TZ01)

Placebo Comparator group

Description:

Participants will receive placebo SC

Treatment:

Drug: Placebo

Retatrutide (RT01)

Experimental group

Description:

Participants will receive retatrutide SC

Treatment:

Drug: Retatrutide

Placebo (RT01)

Placebo Comparator group

Description:

Participants will receive placebo SC

Treatment:

Drug: Placebo