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

Resumen

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.

Elegibilidad

Diseño del estudio

Variables de resultado

1. Variable de resultado principal

   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

   Plazo Baseline up to Study Completion (about 224 weeks)

2. Variable de resultado secundaria

   Change from Baseline in Enhanced Liver Fibrosis (ELF) Score

   Plazo Baseline, Week 104

3. Variable de resultado secundaria

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

   Plazo Baseline, Week 104

4. Variable de resultado secundaria

   Percent Change from Baseline in Liver Fat Content (LFC)

   Plazo Baseline, Week 104

5. Variable de resultado secundaria

   Time to Occurrence of Progression to Cirrhosis

   Plazo Baseline up to Study Completion (about 224 weeks)

6. Variable de resultado secundaria

   Change from Baseline in Aspartate Aminotransferase (AST)

   Plazo Baseline, Study Completion (about 224 weeks)

7. Variable de resultado secundaria

   Change from Baseline in Alanine Aminotransferase (ALT)

   Plazo Baseline, Study Completion (about 224 weeks)

8. Variable de resultado secundaria

   Change from Baseline in Body Weight

   Plazo Baseline, Study Completion (about 224 weeks)

9. Variable de resultado secundaria

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

   Plazo Baseline, Week 104

10. Variable de resultado secundaria

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

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

    Plazo Baseline up to Study Completion (about 224 weeks)

Fechas

Real significa que el evento ocurrió. Estimada significa que el patrocinador lo prevé. Ambas cosas significan algo distinto.

Ubicaciones

481 centros están en reclutamiento

En el registro figuran 513 centros más.

Documentos del estudio

No hay documentos enlazados en este registro.

Cambios a lo largo del tiempo

1. 8 de septiembre de 2026

   Centro eliminado

   2 sites removed (563 total)

   565 → 563

2. 21 de agosto de 2026

   Centro añadido

   1 site added (565 total)

   564 → 565

3. 6 de agosto de 2026

   Centro añadido

   1 site added (564 total)

   563 → 564