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

Phase 3RecruitingNCT06632444

Boehringer Ingelheim1,800 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. 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 2. Diagnosis of MASH (non-alcoholic fatty liver disease (NAFLD)) activity score \[NAS\] ≥4 3. 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 4. Be willing to maintain a stable diet and physical activity levels throughout the entire trial Further inclusion criteria apply Exclusion criteria: 1. 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 2. Any history or evidence of acute or chronic liver disease other than MASH 3. Histologically documented liver cirrhosis (fibrosis stage F4), either at screening or in a historical biopsy 4. History of or current diagnosis of hepatocellular carcinoma 5. History of or planned liver transplant 6. Inability or unwillingness to undergo a liver biopsy at screening (if a suitable historical biopsy is unavailable for central review), or during trial conduct. 7. History of portal hypertension or presence of decompensated liver disease 8. Model for end-stage liver disease (MELD) score ≥12 due to liver disease. Further exclusion criteria apply

Locations (511)

University of Alabama at Birmingham

Birmingham, Alabama, United States

NOT_YET_RECRUITING

The Institute for Liver Health II DBA Arizona Clinical Trials

Peoria, Arizona, United States

RECRUITING

Scottsdale Clinical Trials

Scottsdale, Arizona, United States

RECRUITING

Adobe Clinical Research, LLC

Tucson, Arizona, United States

Outcomes

Primary Outcomes

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.

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

Time frame: Baseline 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 CSPH

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

Time frame: Up to 7 years.

Secondary Outcomes

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

Time frame: Baseline and at Week 52.

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

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

Time frame: Baseline and at Week 52.

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

Time frame: 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)

Time frame: Baseline and at Week 52.

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

Time frame: Baseline and at Week 52.

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

Time frame: At baseline and at Week 114

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

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

Time frame: At baseline and at Week 114

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 114.

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.

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

Time frame: Up to 7 years.

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.

Part 1: Improvement of liver fat content (LFC)

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.

Time frame: At baseline and at Week 52.

Part 2: Improvement of LFC

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.

Time frame: At baseline and at Week 114.

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

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

Time frame: At baseline and at Week 52.

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

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Time frame: 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)

LDL=low-density lipoprotein

Time frame: 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)

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Time frame: At baseline and at Week 114.

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

Time frame: At baseline and at Week 52.

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

Overview

Conditions

Interventions

Eligibility

Locations (511)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts