A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase III Trial Evaluating Long-term Efficacy and Safety of Survodutide Weekly Injections in Adult Participants With Noncirrhotic Non-alcoholic Steatohepatitis/Metabolic Dysfunction-associated Steatohepatitis (NASH/MASH) and (F2) - (F3) Stage of Liver Fibrosis

Official 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 vi

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 1,800 participants

Study Arms

• Survodutide (EXPERIMENTAL)
• Placebo (PLACEBO_COMPARATOR)

Interventions

• COMBINATION_PRODUCT: Survodutide — Subcutaneous injection, prefilled syringe
• COMBINATION_PRODUCT: Placebo — Subcutaneous injection, prefilled syringe

Primary Outcomes

• Part 1: Resolution of MASH without worsening of liver fibrosis on MASH Clinical Research Network (CRN) fibrosis score (Baseline and at Week 52.)
• Part 1: At least a 1-point improvement in fibrosis stage with no worsening of MASH (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 (Up to 7 years.)

Secondary Outcomes

• 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 glycosylated haemoglobin (HbA1c) [%] (Baseline and at Week 52.)
• Key secondary endpoint part 1: Absolute change from baseline in enhanced liver fibrosis (ELF) score (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.)

Eligibility Criteria

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

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• The Institute for Liver Health II DBA Arizona Clinical Trials, Peoria, Arizona, United States
• Scottsdale Medical Specialists, Ltd, Scottsdale, Arizona, United States
• Adobe Clinical Research, LLC, Tucson, Arizona, United States
• Arizona Liver Health - Tucson, Tucson, Arizona, United States
• Del Sol Research Management, LLC, Tucson, Arizona, United States
• Hope Clinical Research, Canoga Park, California, United States
• Velocity Clinical Research-Chula Vista, Chula Vista, California, United States
• Southern California Research Center, Coronado, California, United States
• ARK Clinical Research, Fountain Valley, California, United States
• ...and 10 more locations

Contact Information

• Boehringer Ingelheim — CONTACT
  Phone: 1-800-243-0127
  Email: clintriage.rdg@boehringer-ingelheim.com

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