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

Résumé

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.

Éligibilité

Conception de l'étude

Critères de jugement

1. Critère de jugement 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

   Délai Baseline up to Study Completion (about 224 weeks)

2. Critère de jugement secondaire

   Change from Baseline in Enhanced Liver Fibrosis (ELF) Score

   Délai Baseline, Week 104

3. Critère de jugement secondaire

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

   Délai Baseline, Week 104

4. Critère de jugement secondaire

   Percent Change from Baseline in Liver Fat Content (LFC)

   Délai Baseline, Week 104

5. Critère de jugement secondaire

   Time to Occurrence of Progression to Cirrhosis

   Délai Baseline up to Study Completion (about 224 weeks)

6. Critère de jugement secondaire

   Change from Baseline in Aspartate Aminotransferase (AST)

   Délai Baseline, Study Completion (about 224 weeks)

7. Critère de jugement secondaire

   Change from Baseline in Alanine Aminotransferase (ALT)

   Délai Baseline, Study Completion (about 224 weeks)

8. Critère de jugement secondaire

   Change from Baseline in Body Weight

   Délai Baseline, Study Completion (about 224 weeks)

9. Critère de jugement secondaire

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

   Délai Baseline, Week 104

10. Critère de jugement secondaire

    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

    Délai Baseline up to Study Completion (about 224 weeks)

Dates

Réelle signifie que l'événement a eu lieu. Estimée signifie que le promoteur s'y attend. Les deux ont un sens différent.

Lieux

481 sites sont en recrutement

513 sites supplémentaires sont indiqués dans la fiche du registre.

Documents de l'étude

Aucun document n'est lié dans cette fiche du registre.

Évolution au fil du temps

1. 8 septembre 2026

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2. 21 août 2026

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3. 6 août 2026

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