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

NCT06632457
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
1,590
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Lead sponsor
Boehringer Ingelheim
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Start date
2024-11-12
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Number of sites
445
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Summary
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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Short title
LIVERAGE™ - Cirrhosis: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Cirrhosis
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Official 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
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2029-06-05
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First posted
2024-10-09
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Registry last updated
2026-08-21
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Primary completion date
2029-06-05
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Start date
2024-11-12
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Participants
1,590
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Participant count basis
Estimated
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Planned participants
1,590
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Protocol amendments
4
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Number of sites
445
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Boehringer Ingelheim
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06632457
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ClinicalTrials.gov ID
NCT06632457
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

  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

    Timeframe: up to 4.5 years.

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

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

    Timeframe: At baseline and at Week 76.

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

    Timeframe: 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

    Timeframe: 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)

    Timeframe: At baseline and at Week 76.

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

    Timeframe: At baseline and at Week 76.

  6. Time to first occurrence of progression to CSPH

    Timeframe: 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

    Timeframe: up to 4.5 years.

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

    Timeframe: 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)

    Timeframe: up to 4.5 years.

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

    Timeframe: At baseline and at Week 76.

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

    Timeframe: At baseline and at Week 76.

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

    Timeframe: At baseline and at Week 76.

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

    Timeframe: At baseline and at Week 76.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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.
  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 ≤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.

  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:

    • 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
    • PLT <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)) or history of chronic HBV infection

  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

Sources for eligibility
clinicaltrials.gov

  • The Institute for Liver Health II DBA Arizona Clinical TrialsPeoria, United StatesRecruiting
  • Scottsdale Medical Specialists, LtdScottsdale, United StatesRecruiting
  • Adobe Clinical Research, LLCTucson, United StatesRecruiting
  • Arizona Liver Health - TucsonTucson, United StatesRecruiting
  • Del Sol Research Management, LLCTucson, United StatesRecruiting
  • Hope Clinical ResearchCanoga Park, United StatesRecruiting
  • Velocity Clinical Research-Chula VistaChula Vista, United StatesRecruiting
  • Southern California Research CenterCoronado, United StatesRecruiting
  • ARK Clinical ResearchFountain Valley, United StatesRecruiting
  • Velocity Clinical Research-Huntington ParkHuntington Park, United StatesRecruiting
  • 310 Clinical ResearchInglewood, United StatesRecruiting
  • Velocity Clinical Research, San DiegoLa Mesa, United StatesRecruiting
  • Om Research, LLCLancaster, United StatesRecruiting
  • Catalina Research Institute, LLCMontclair, United StatesRecruiting
  • Clinnova Research SolutionsOrange, United StatesRecruiting
  • Fomat Medical ResearchOxnard, United StatesRecruiting
  • Cadena Care Institute, LLCPoway, United StatesRecruiting
  • Ficramed Research InstitutePoway, United StatesRecruiting
  • Inland Empire Clinical Trials, LLCRialto, United StatesRecruiting
  • Metro Clinical TrialsSan Bernardino, United StatesRecruiting
  • Acclaim Clinical ResearchSan Diego, United StatesRecruiting
  • Future Innovative TreatmentsColorado Springs, United StatesRecruiting
  • South Denver Gastroenterology PCEnglewood, United StatesRecruiting
  • Connecticut Gastroenterology Clinical Research FoundationBristol, United StatesRecruiting
  • Synergy HealthcareBradenton, United StatesRecruiting

And 420 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2024-513741-36-00
  • U1111-1307-0227
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)

Targets (2)