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

Boehringer Ingelheim

Status and phase: Enrolling; Phase 3

Conditions: Metabolic Dysfunction Associated Steatohepatitis

Treatments: Drug: Survodutide; Drug: Placebo matching survodutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06632457

U1111-1307-0227 (Registry Identifier)

1404-0064

2024-513741-36-00 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,590 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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
2. Body mass index (BMI) ≥27 kg/m2(≥25 kg/m2 for Asian trial participants)
3. Compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis diagnosed according to modified Liver Forum criteria (Noureddin et al, Gastroenterology 2020;159:422-427).
4. 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 or FibroScan® with CAP ≤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.
5. Further inclusion criteria apply.

Exclusion criteria

1. 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.

2. Model of end-stage liver Disease (MELD) score >12 due to liver disease

3. History or current (i.e. at screening) hepatic decompensation event of any of the following but not limited to:

   • History of portal hypertension-related upper gastrointestinal (GI) bleeding
   • Ascites
   • Hepatic encephalopathy (HE) ≥Grade 1 according to the West Haven criteria

4. 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
   • Platelet count <100,000/µL (<100 GI/L)

5. 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

6. Hepatitis B positive (defined as positive hepatitis B surface antigen (HBsAg))

7. Hepatitis C positive (defined as positive hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA))

8. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >5x ULN

9. Evidence of alcoholic liver disease, or drug-induced liver disease, as defined on the basis of typical exposure and history

10. History of liver transplantation or listed for liver transplantation

11. History of transjugular intrahepatic portosystemic shunt (TIPS) or other radiological/surgical procedure for portal hypertension treatment

12. Further exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,590 participants in 2 patient groups, including a placebo group

Survodutide

Experimental group

Treatment:

Drug: Survodutide

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo matching survodutide