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NCT Number: NCT06632444

LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Moderate or Advanced Liver Fibrosis

This study is open to adults who are at least 18 years old living with obesity and have:

* a confirmed liver disease called non-alcoholic steatohepatitis (NASH)/metabolic associated steatohepatitis (MASH) and * moderate or advanced liver fibrosis

People with a history of acute or chronic liver diseases other than MASH or chronic alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with MASH and moderate or advanced liver fibrosis improve their liver function.

This study has 2 parts. The purpose of the first part of this study is to find out the effect of survodutide on MASH and liver fibrosis. The purpose of the second part is to find out how safe and effective survodutide is in improving liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. The survodutide doses are slowly increased until the target dose is reached. All participants receive counselling to make changes to their diet and to exercise regularly.

Participants are in the study for up to 7 years. During this time, they regularly visit the study site or have remote visits by video call. For about the first year of the study, participants have these visits every 2 weeks, increasing to every 4 weeks and then every 6 weeks. After being in the study for a little over a year participants will then alternate between visiting the study site or having a remote visit every 3 months until the end of the study.

The doctors check participants' health and take note of any unwanted effects. The participants' body weight and effects on the stomach and intestines are regularly measured. At some visits the liver is measured using different imaging methods. At 2 or 3 visits doctors take a small sample of liver tissue (biopsy). The participants also fill in questionnaires about their symptoms and quality of life. The results are compared between the groups to see whether the treatment works.

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Key information

Conditions

Metabolic Dysfunction Associated Steatohepatitis (MASH) Digestive System Diseases Fibrosis Liver Cirrhosis Liver Diseases Liver Fibrosis Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Buenos Aires Macula S.A., Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female participants ≥18 years (or who are of legal age in countries where that is greater than 18 years) of age at time of consent
  • Diagnosis of MASH (non-alcoholic fatty liver disease (NAFLD)) activity score [NAS] ≥4
  • Stable body weight defined as less than 5% self-reported change in body weight 3 months prior to the screening or during the period between the historical biopsy and randomisation, if a historical biopsy is used
  • Be willing to maintain a stable diet and physical activity levels throughout the entire trial Further inclusion criteria apply

Exclusion criteria

  • Any of the following liver laboratory test abnormalities at screening:
  • Serum AST and/or alanine aminotransferase (ALT) elevation ≥5x upper limit of normal (ULN)
  • Platelet count <140 000/mm^3 (<140 GI/L)
  • Alkaline phosphatase >2x upper limit of normal (ULN)
  • Abnormal synthetic liver function as defined by screening central laboratory evaluation:
  • Albumin below <3.5 g/dL (35.0 g/L)
  • OR International normalised ratio (INR) of prothrombin time >1.3
  • OR total serum bilirubin concentration ≥1.5x ULN
  • Any history or evidence of acute or chronic liver disease other than MASH
  • Histologically documented liver cirrhosis (fibrosis stage F4), either at screening or in a historical biopsy
  • History of or current diagnosis of hepatocellular carcinoma
  • History of or planned liver transplant
  • Inability or unwillingness to undergo a liver biopsy at screening (if a suitable historical biopsy is unavailable for central review), or during trial conduct.
  • History of portal hypertension or presence of decompensated liver disease
  • Model for end-stage liver disease (MELD) score ≥12 due to liver disease. Further exclusion criteria apply

Treatment and study plan

Survodutide

Combination Product

Subcutaneous injection, prefilled syringe

Other names: BI 456906

Placebo

Combination Product

Subcutaneous injection, prefilled syringe

Primary outcomes

  1. Part 1: Resolution of MASH without worsening of liver fibrosis on MASH Clinical Research Network (CRN) fibrosis score

    Time frame: Baseline and at Week 52.

  2. Part 1: At least a 1-point improvement in fibrosis stage with no worsening of MASH

    Time frame: Baseline and at Week 52.

  3. Part 2: Time to first occurrence of any of components of the composite endpoint consisting of progression to cirrhosis, all-cause mortality, liver transplant, hepatic decompensation event(s), worsening of MELD score to ≥15, progression to CSPH

    Time frame: Up to 7 years.

    Progression to cirrhosis is defined as histological fibrosis score CRN F4. MELD = Model for End-stage Liver Disease CSPH =clinically significant portal hypertension

Secondary outcomes

  1. Key secondary endpoint part 1: Percentage change from baseline in body weight [kg]

    Time frame: Baseline and at Week 52.

  2. Key secondary endpoint part 1: Absolute change from baseline in glycosylated haemoglobin (HbA1c) [%]

    Time frame: Baseline and at Week 52.

    This endpoint is specified only for the participants with type 2 diabetes mellitus.

  3. Key secondary endpoint part 1: Absolute change from baseline in enhanced liver fibrosis (ELF) score

    Time frame: Baseline and at Week 52.

  4. Key secondary endpoint part 1: Absolute change from baseline in liver stiffness [kPa] assessed by vibration-controlled transient elastography (VCTE)

    Time frame: Baseline and at Week 52.

  5. Key secondary endpoint part 1: Achievement of no progression of fibrosis assessed by central pathology (yes/no)

    Time frame: Baseline and at Week 52.

  6. Key secondary endpoint part 2: Percentage change from baseline in body weight [kg]

    Time frame: At baseline and at Week 114

  7. Key secondary endpoint part 2: Absolute change from baseline in HbA1c [%]

    Time frame: At baseline and at Week 114

    This endpoint is specified only for the participants with type 2 diabetes mellitus.

  8. Key secondary endpoint part 2: Absolute change from baseline in ELF score

    Time frame: At baseline and at Week 114.

  9. Key secondary endpoint part 2: Absolute change from baseline in liver stiffness [kPa] assessed by VCTE

    Time frame: At baseline and at Week 114.

  10. Key secondary endpoint part 2: Achievement of no progression of fibrosis assessed by central pathology (yes/no)

    Time frame: At baseline and at 7 years.

  11. Key secondary endpoint part 2: Occurrence of all-cause hospitalisation (first and recurrent)

    Time frame: Up to 7 years.

  12. Key secondary endpoint part 2: Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE)5-point major adverse cardiac event (5P-MACE)

    Time frame: Up to 7 years.

  13. Part 1: Improvement of liver fat content (LFC)

    Time frame: At baseline and at Week 52.

    Defined as at least 30% relative reduction in LFC compared with baseline assessed by Magnetic resonance imaging proton density fat fraction (MRI-PDFF).

    This endpoint will be reported only for a subset of participants in the MRI sub-study.

  14. Part 2: Improvement of LFC

    Time frame: At baseline and at Week 114.

    Defined as at least 30% relative reduction in LFC compared with baseline assessed by MRI-PDFF.

    This endpoint will be reported only for a subset of participants in the MRI sub-study.

  15. Part 1: Absolute change from baseline in LFC [%] in MRI-PDFF

    Time frame: At baseline and at Week 52.

    This endpoint will be reported only for a subset of participants in the MRI sub-study.

  16. Part 2: Absolute change from baseline in LFC [%] in MRI-PDFF

    Time frame: At baseline and at Week 114.

    This endpoint will be reported only for a subset of participants in the MRI sub-study.

  17. Part 1: Absolute change from baseline in alanine aminotransferase (ALT) [U/L]

    Time frame: At baseline and at Week 52.

  18. Part 2: Absolute change from baseline in alanine aminotransferase (ALT) [U/L]

    Time frame: At baseline and at Week 114.

  19. Part 1: Absolute change from baseline in aspartate aminotransferase (AST) [U/L]

    Time frame: At baseline and at Week 52.

  20. Part 2: Absolute change from baseline in aspartate aminotransferase (AST) [U/L]

    Time frame: At baseline and at Week 114.

  21. Part 1: Absolute change from baseline in systolic blood pressure (SBP) [mmHg]

    Time frame: At baseline and at Week 52.

  22. Part 2: Absolute change from baseline in systolic blood pressure (SBP) [mmHg]

    Time frame: At baseline and at Week 114.

  23. Part 1: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg]

    Time frame: At baseline and at Week 52.

  24. Part 2: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg]

    Time frame: At baseline and at Week 114.

  25. Part 1: Absolute changes from baseline in lipids [mg/dL] (including but not limited to: total cholesterol, LDL cholesterol, very low-density lipoprotein [VLDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides)

    Time frame: At baseline and at Week 52.

    LDL=low-density lipoprotein

  26. Part 2: Absolute changes from baseline in lipids [mg/dL] (including but not limited to: total cholesterol, LDL cholesterol, very low-density lipoprotein [VLDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides)

    Time frame: At baseline and at Week 114.

  27. Part 1: Absolute change from baseline in free fatty acids [mg/dL]

    Time frame: At baseline and at Week 52.

  28. Part 2: Absolute change from baseline in free fatty acids [mg/dL]

    Time frame: At baseline and at Week 114.

  29. Part 1: Progression to cirrhosis (defined as histological fibrosis score CRN F4) (yes/no)

    Time frame: At baseline and at Week 52.

Study contacts

Contact information is provided by the study sponsor or research team.

Boehringer Ingelheim

CONTACT

[email protected]

1-800-243-0127

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase III Trial Evaluating Long-term Efficacy and Safety of Survodutide Weekly Injections in Adult Participants With Noncirrhotic Non-alcoholic Steatohepatitis/Metabolic Dysfunction-associated Steatohepatitis (NASH/MASH) and (F2) - (F3) Stage of Liver Fibrosis

Important dates

Study start
2024
Primary completion
2031
Study completion
2031
First posted
Oct 9, 2024
Registry last updated
Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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