Metabolic Dysfunction-Associated Steatotic Liver Disease
Conditions
Keywords
Nonalcoholic Steatohepatitis, NASH, Fatty Liver, Fatty Liver Disease, SLD, Metabolic Dysfunction-Associated Fatty Liver Disease, MAFLD, Non-alcoholic Fatty Liver Disease, NAFLD, Hepatic Steatosis, Liver Related Outcomes, GLP1, Incretin, Non-Invasive Test
Brief 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.
Interventions
DRUGTirzepatide
Administered SC
DRUGRetatrutide
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Enhanced Liver Fibrosis (ELF) Score | Baseline, Week 104 | — |
| Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM) | Baseline, Week 104 | — |
| Percent Change from Baseline in Liver Fat Content (LFC) | Baseline, Week 104 | — |
| Time to Occurrence of Progression to Cirrhosis | Baseline up to Study Completion (about 224 weeks) | — |
| Change from Baseline in Aspartate Aminotransferase (AST) | Baseline, Study Completion (about 224 weeks) | — |
| Change from Baseline in Alanine Aminotransferase (ALT) | Baseline, Study Completion (about 224 weeks) | — |
| Change from Baseline in Body Weight | Baseline, Study Completion (about 224 weeks) | — |
| Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK) | Baseline, Week 104 | — |
| Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3) | Baseline up to Study Completion (about 224 weeks) | MACE-3 composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death |
Countries
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, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed