Recruiting NCT07165028

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

Phase III Interventional Metabolic Dysfunction-Associated Steatotic Liver Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Tirzepatide, Retatrutide, Placebo.
Who it may be relevant to: Registry conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +29
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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

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.

Interventions

Drug Tirzepatide
Administered SC
Drug Retatrutide
Administered SC
Drug Placebo
Administered SC

Primary outcome measures

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)]

Secondary outcome measures (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)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Single blind
Primary purpose: Treatment