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NCT Number: NCT06632457

LIVERAGE™ - Cirrhosis: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Cirrhosis

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

* A confirmed liver disease called non-alcoholic steatohepatitis (NASH) or * A confirmed liver disease called metabolic-associated steatohepatitis (MASH) * BMI of 27 kg/m2 or more or * 25 kg/m2 or more if the participant is Asian.

People with a history of other chronic liver diseases or high 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 NASH or MASH improve their 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. All participants regularly receive counselling to make changes to their diet and to exercise regularly.

Participants are in the study for up to 4 and a half years. During this time, they visit the study site or have a remote visit by video call every 2, 4 or 6 weeks for about a 1 year and 5 months. After this time participants visit the trial site or have 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 is regularly measured. At some visits the liver parameters are measured using different imaging methods. The participants also fill in questionnaires about their symptoms. The results are compared between the groups to see whether the treatment works.

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Key information

Conditions

Metabolic Dysfunction Associated Steatohepatitis

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 adults ≥18 years of age at the time of screening, and at least the legal age of consent in countries where it is >18 years
  • Body mass index (BMI) ≥27 kg/m2(≥25 kg/m2 for Asian trial participants)
  • Compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis.
  • Magnetic resonance imaging proton density fat fraction (MRI-PDFF) fat fraction ≥5% or FibroScan® with controlled attenuation parameter (CAP) ≥288 dB/m, obtained during the screening period or a historic MRI-PDFF ≤12 weeks prior to randomisation (except for patients with 'cryptogenic cirrhosis' where MRI-PDFF <5% or FibroScan® with CAP <288 dB/m is allowed). This inclusion criterion does not apply for participants with a recent (≤12 months prior to randomisation) liver biopsy showing steatosis/steatohepatitis.
  • Further inclusion criteria apply.

Exclusion criteria

  • Current or history (<5 years) of significant alcohol consumption, defined as an average of >140 g/week in female patients and >210 g/week in male patients, for a period of >3 consecutive months, or an inability to reliably quantify alcohol consumption based upon judgment of the investigator.
  • Model of end-stage liver Disease (MELD) score >12 due to liver disease
  • History or current (i.e. at screening) hepatic decompensation event of any of the following but not limited to:
  • Portal hypertension-related upper gastrointestinal (GI) bleeding
  • Ascites
  • Hepatic encephalopathy (HE) ≥Grade 1 according to the West Haven criteria
  • Any of the following lab test result at screening
  • Albumin below <3.5 g/dL (<35.0 g/L)
  • International normalised ratio (INR) >1.3 unless due to therapeutic anticoagulants
  • Total bilirubin (TBL) >1.2x upper limit of normal (ULN) NOTE: Trial participants with Gilbert Syndrome are eligible with a TBL >1.2x ULN if reticulocyte count is within normal limits, haemoglobin is within normal limits unless due to chronic anaemia and unrelated to haemolysis, and direct bilirubin is <20% of TBL.
  • Alkaline phosphatase >1.5x ULN
  • PLT <100,000/µL (<100 GI/L)
  • History or evidence of other chronic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis or overlap syndrome, Wilson's disease, alpha-1-antitrypsin deficiency, or genetic haemochromatosis
  • Hepatitis B positive (defined as positive hepatitis B surface antigen (HBsAg)) or history of chronic HBV infection
  • Hepatitis C positive (defined as positive hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA))
  • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >5x ULN
  • Evidence of alcoholic liver disease, or drug-induced liver disease, as defined on the basis of typical exposure and history
  • History of liver transplantation or listed for liver transplantation
  • History of transjugular intrahepatic portosystemic shunt (TIPS) or other radiological/surgical procedure for portal hypertension treatment
  • Further exclusion criteria apply

Treatment and study plan

Survodutide

Combination Product

Subcutaneous injection, pre-filled syringe

Other names: BI 456906

Placebo matching survodutide

Combination Product

Subcutaneous injection, pre-filled syringe

Primary outcomes

  1. Time to first occurrence of any component of the composite clinical endpoint (at EoS) consisting of: all-cause mortality, liver transplant, hepatic decompensation events, worsening of MELD score to ≥15 and progression to CSPH

    Time frame: up to 4.5 years.

    MELD = model of end-stage liver disease CSPH = Clinically significant portal hypertension

Secondary outcomes

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

    Time frame: At baseline and at Week 76.

  2. Key secondary endpoint: Percentage change from baseline in body weight

    Time frame: At baseline and at Week 76.

  3. Key secondary endpoint: Absolute change from baseline in glycosylated haemoglobin A1c (HbA1c) (%) in participants with type 2 diabetes mellitus (T2DM) at baseline

    Time frame: At baseline and at Week 76.

  4. Key secondary endpoint: Absolute change from baseline in liver stiffness (kPa) in FibroScan® vibration-controlled transient elastography (VCTE)

    Time frame: At baseline and at Week 76.

  5. Percentage change from baseline in liver stiffness in FibroScan® VCTE

    Time frame: At baseline and at Week 76.

  6. Time to first occurrence of progression to CSPH

    Time frame: up to 4.5 years.

  7. Time to first occurrence of any of the hepatic decompensation events (ascites, HE, or portal hypertension-related upper GI bleeding), or worsening of MELD score to ≥15

    Time frame: up to 4.5 years.

  8. Occurrence of all-cause hospitalisation (first and recurrent)

    Time frame: up to 4.5 years.

  9. Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE)

    Time frame: up to 4.5 years.

  10. Absolute changes from baseline in lipids (mg/dL)

    Time frame: At baseline and at Week 76.

  11. Absolute change from baseline in aspartate aminotransferase (AST) (U/L)

    Time frame: At baseline and at Week 76.

  12. Absolute change from baseline in alanine aminotransferase (ALT) (U/L)

    Time frame: At baseline and at Week 76.

  13. Absolute change from baseline in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)

    Time frame: At baseline and at Week 76.

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 Phase III Double-blind, Randomised, Placebo-controlled Trial to Evaluate Liver-related Clinical Outcomes and Safety of Once Weekly Injected Survodutide in Participants With Compensated Non-alcoholic Steatohepatitis/Metabolic Dysfunction Associated Steatohepatitis (NASH/MASH) Cirrhosis

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
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.