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

Phase 3
Recruiting
Conditions
Metabolic Dysfunction Associated Steatohepatitis (MASH)
Liver Fibrosis
Interventions
Drug: Placebo
Registration Number
NCT06632444
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1800
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SurvodutideSurvodutide-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Part 1: Resolution of MASH without worsening of liver fibrosis on MASH Clinical Research Network (CRN) fibrosis scoreBaseline and at Week 52.
Part 1: At least a 1-point improvement in fibrosis stage with no worsening of MASHBaseline and at Week 52.
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 CSPHUp 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 Outcome Measures
NameTimeMethod
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)Up to 7 years.
Part 1: Improvement of liver fat content (LFC)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.

Part 2: Improvement of LFCAt 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.

Part 2: Absolute change from baseline in LFC [%] in MRI-PDFFAt baseline and at Week 114.

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

Part 2: Absolute change from baseline in systolic blood pressure (SBP) [mmHg]At baseline and at Week 114.
Part 1: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg]At baseline and at Week 52.
Part 2: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg]At baseline and at Week 114.
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)At baseline and at Week 52.

LDL=low-density lipoprotein

Part 1: Progression to cirrhosis (defined as histological fibrosis score CRN F4) (yes/no)At baseline and at Week 52.
Key secondary endpoint part 1: Percentage change from baseline in body weight [kg]Baseline and at Week 52.
Key secondary endpoint part 1: Absolute change from baseline in liver stiffness [kPa] assessed by vibration-controlled transient elastography (VCTE)Baseline and at Week 52.
Key secondary endpoint part 1: Achievement of no progression of fibrosis assessed by central pathology (yes/no)Baseline and at Week 52.
Key secondary endpoint part 2: Percentage change from baseline in body weight [kg]At baseline and at Week 114
Key secondary endpoint part 2: Absolute change from baseline in HbA1c [%]At baseline and at Week 114

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

Key secondary endpoint part 2: Absolute change from baseline in ELF scoreAt baseline and at Week 114.
Key secondary endpoint part 2: Absolute change from baseline in liver stiffness [kPa] assessed by VCTEAt baseline and at Week 114.
Key secondary endpoint part 2: Achievement of no progression of fibrosis assessed by central pathology (yes/no)At baseline and at 7 years.
Key secondary endpoint part 2: Occurrence of all-cause hospitalisation (first and recurrent)Up to 7 years.
Part 1: Absolute change from baseline in LFC [%] in MRI-PDFFAt baseline and at Week 52.

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

Part 1: Absolute change from baseline in alanine aminotransferase (ALT) [U/L]At baseline and at Week 52.
Part 2: Absolute change from baseline in alanine aminotransferase (ALT) [U/L]At baseline and at Week 114.
Part 1: Absolute change from baseline in aspartate aminotransferase (AST) [U/L]At baseline and at Week 52.
Part 2: Absolute change from baseline in aspartate aminotransferase (AST) [U/L]At baseline and at Week 114.
Part 1: Absolute change from baseline in systolic blood pressure (SBP) [mmHg]At baseline and at Week 52.
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)At baseline and at Week 114.
Part 1: Absolute change from baseline in free fatty acids [mg/dL]At baseline and at Week 52.
Part 2: Absolute change from baseline in free fatty acids [mg/dL]At baseline and at Week 114.
Key secondary endpoint part 1: Absolute change from baseline in glycosylated haemoglobin (HbA1c) [%]Baseline and at Week 52.

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

Key secondary endpoint part 1: Absolute change from baseline in enhanced liver fibrosis (ELF) scoreBaseline and at Week 52.

Trial Locations

Locations (468)

Arizona Liver Health - Tucson

🇺🇸

Tucson, Arizona, United States

Velocity Clinical Research

🇺🇸

Huntington Park, California, United States

Lake Center for Clinical Research

🇺🇸

Lady Lake, Florida, United States

CIPREC

🇦🇷

Ciudad Autonoma de Buenos Aire, Argentina

Ordensklinikum Linz GmbH

🇦🇹

Linz, Austria

Okayama University Hospital

🇯🇵

Okayama, Japan

Emc Instytut Medyczny S.A.

🇵🇱

Wroclaw, Poland

Fondazione Epatocentro Ticino

🇨🇭

Arzo, Switzerland

Uludag Universitesi Tip Fakultesi

🇹🇷

Bursa, Turkey

Cambridge University Hospitals NHS Foundation Trust

🇬🇧

Cambridge, United Kingdom

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Arizona Liver Health - Tucson
🇺🇸Tucson, Arizona, United States
Boehringer Ingelheim
Contact
833-602-2368
unitedstates@bitrialsupport.com

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