Study to evaluate whether survodutide can help people with a liver disease known as NASH/MASH with moderate or advanced liver fibrosis

Critères de participation
To be eligible, all inclusion criteria must receive a positive response during screening and must be reconfirmed at baseline (i.e., before randomization), except for laboratory tests for which screening results are used for randomization: 1. Male or female participants aged ≥18 years (or of legal age in countries where the age of majority is above 18 years) at the time of consent. 2. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) (non-alcoholic steatohepatitis activity score [NAS] ≥4, with at least 1 point each for inflammation and ballooning) and F2–F3 stage fibrosis confirmed by a biopsy performed during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization. 3. Stable body weight, defined as self-reported body weight variation of less than 5% months before screening or during the period between the historical biopsy and randomization if a historical biopsy is used. 4. Participants will be randomized according to the following screening parameters that must be met in consecutive order: aspartate aminotransferase (AST) >20 U/l, liver stiffness measured by vibration-controlled transient elastography (VCTE) FibroScan® ≥7.5 kPa, and FibroScan-AST (FAST) >0.36 at Visit 1 and hepatic fat fraction ≥8% measured by proton density fat fraction MRI (MRI-PDFF) before scheduling the screening biopsy. 5. Willingness to maintain a stable diet and levels of physical activity throughout the duration of the trial. 6. Written informed consent, signed and dated, in accordance with good clinical practice of the International Conference on Harmonisation (ICH-GCP) and local legislation prior to entering the trial. 7. Women of childbearing potential must be willing and able to use highly effective contraceptive methods, according to ICH M3(R2) guidelines, which have a low failure rate of less than 1% per year when used consistently and correctly. A list of contraceptive methods that meet these criteria and instructions on the duration of their use are provided in the participant information and Appendix 10.3. 8. In the investigator's judgment, subjects are well motivated, capable, and willing to: • Learn to self-inject the investigational medicinal product (IMP), as required for this protocol (individuals with physical limitations who are unable to perform the injections must have assistance from a qualified person to inject the IMP) • Inject the IMP or accept the injection from a qualified assistant • Follow the trial procedures throughout its duration, including, but not limited to: following lifestyle advice (e.g., dietary restrictions and exercise program), keeping a diary, completing required questionnaires, and managing the IMP as described in the instructions for use (IFU) (BASEC)

Critères d'exclusion
To be eligible, all of the following exclusion criteria must receive a negative response during screening and must be reconfirmed at baseline (i.e., before randomization), except for laboratory tests for which screening results are used for randomization: Liver-related: 1. Any abnormality in liver laboratory tests at screening 2. Any history or evidence of acute or chronic liver disease other than MASH, including, but not limited to: • Viral hepatitis, unless eradicated at least 3 years prior to screening • Evidence of drug-induced liver disease or alcoholic liver disease, defined based on typical exposure and history. • Autoimmune hepatitis • Wilson's disease • Hemochromatosis • Primary biliary cholangitis • Primary sclerosing cholangitis • Alpha-1-antitrypsin deficiency 3. Histologically documented liver cirrhosis (F4 stage fibrosis), at screening or in a historical biopsy 4. Current or past history of hepatocellular carcinoma 5. History of liver transplant or scheduled transplant 6. Inability or unwillingness to undergo a liver biopsy at screening or during the conduct of the trial 7. History of portal hypertension or presence of decompensated liver disease (including hepatic encephalopathy, variceal bleeding, ascites, and spontaneous bacterial peritonitis) 8. Mayo score for end-stage liver disease (MELD) ≥12 due to liver disease Obesity 9. Treatment with any medication for obesity indication in the 3 months prior to the screening biopsy or the time point of the historical biopsy 10. Previous or planned treatment (during the trial period) for obesity with surgery or a weight loss device, or previous GI tract surgery that, in the investigator's judgment, could interfere with body weight. 11. Present obesity induced by other endocrinological disorders Blood sugar: 12. HbA1c >10% (>86 mmol/mol) measured by the central laboratory at screening 13. History of type I diabetes mellitus or any other type other than type 2 14. In patients with uncontrolled and potentially unstable type II diabetes mellitus, diabetic retinopathy or maculopathy, verified by an eye examination in the 3 months prior to screening or during the period between screening and randomization Other medical aspects: 18. Impaired renal function 19. Known and clinically significant gastric emptying anomaly (e.g., severe diabetic gastroparesis or gastric outlet obstruction) 20. Uncontrolled hypo- or hyperthyroidism at screening 21. History of chronic or acute pancreatitis or elevated lipase or amylase >2x ULN measured by the central laboratory at screening 22. Uncontrolled hypertension (mean SBP ≥160 mmHg and/or mean DBP ≥100 mmHg) at screening 23. Trial participants demonstrating recent evidence (in the 6 months prior to screening) of acute or unstable cardiovascular events, e.g., hospitalization for heart failure, acute coronary syndrome, unstable angina, myocardial infarction, ischemic or hemorrhagic stroke, transient ischemic attack, and/or acute peripheral vascular event 26. History of HIV infection or positive HIV test at screening 27. Major surgery performed in the 3 months prior to screening or scheduled during the trial 28. Personal or family history of medullary thyroid carcinoma or MEN 2 29. Calcitonin ≥100 pg/ml (29.26 pmol/l) at screening 30. Confirmed diagnosis of neoplasia (including remission) in the 5 years prior to screening, except for successfully treated basal cell or squamous cell carcinoma. Participants currently under evaluation for neoplasia are not eligible to participate in the trial. 31. History of active autoimmune disease 33. History of organ transplant or awaiting organ transplant. 34. Pregnant women, breastfeeding, or planning to become pregnant during the trial 35. Known or suspected hypersensitivity to the IMP or related products Other exclusions: 40. Currently enrolled in another trial involving an investigational device or drug, or less than 60 days or 5 half-lives, whichever is longer, from the end of another trial involving an investigational device or drug or receiving another experimental treatment(s); current or previous enrollment in strictly observational trials is allowed. If the participant has participated in a previous clinical trial aimed at evaluating treatment for MASH, weight loss, and/or T2DM, there must be a 6-month window before the screening biopsy or the date of the historical biopsy. 41. Previous randomization in this trial 42. Active severe medical condition with a likely life expectancy of <2 years (BASEC)