a study to test whether survodutide helps people living with obesity or overweight and with a confirmed or presumed liver disease called non-alcoholic steatohepatitis (nash) to reduce liver fat and to lose weight

Conditions: Obesity; Non-Alcoholic SteatoHepatitis (NASH)

Summary: this study is open to adults who are at least 18 years old and have * presumed or confirmed nash together with overweight or obesity and * a body mass index (bmi) of 30 kg/m² or more, or * a bmi of 27 kg/m² and at least one weight-related health problem. people with a history of other chronic liver diseases cannot take part in this study. the purpose of this study is to find out whether a medicine called survodutide helps people living with obesity or overweight and a confirmed or presumed liver disease called nonalcoholic steatohepatitis (nash) to have less liver fat and to lose weight. participants are put into 2 groups randomly, which means by chance. 1 group gets different doses of survodutide and 1 group gets placebo. placebo looks like survodutide but does not contain any medicine. every participant has a 2 in 3 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 for about 1 year. in addition to the study medicine, all participants receive counselling to make changes to their diet and to exercise regularly. participants are in the study for about 1 year and 3 months. during this time, it is planned that participants visit the study site up to 14 times and receive 3 phone calls by the site staff. the doctors check participants' health and take note of any unwanted effects. the participants' body weight is regularly measured. at 3 of the visits, the participants' liver is measured using different imaging methods. the results are compared between the groups to see whether the treatment works.


Eligibility criteria:
key inclusion criteria: * age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is \>18 years * bmi ≥30 kg/m², or bmi ≥27 kg/m² and at least one of the following weight-related comorbidities at screening: * hypertension (defined as repeated, i.e. at least 3 measurements in resting condition, systolic blood pressure (sbp) values of ≥140 mmhg and/or diastolic blood pressure (dbp) values of ≥90 mmhg in the absence of anti-hypertensive treatment, or intake of at least 1 antihypertensive drug to maintain a normotensive blood pressure) * dyslipidaemia (defined as at least 1 lipid-lowering treatment required to maintain normal blood lipid levels, or lowdensity lipoprotein (ldl) cholesterol ≥160 mg/dl (≥4.1 mmol/l) or triglycerides ≥150 mg/dl (≥1.7 mmol/l), or high-density lipoprotein (hdl) cholesterol \<40 mg/dl (\<1.0 mmol/l) for men or hdl cholesterol \<50 mg/dl (\<1.3 mmol/l) for women * obstructive sleep apnoea * cardiovascular disease (e.g. heart failure with new york heart association (nyha) functional class ii-iii, history of ischaemic or haemorrhagic stroke or cerebrovascular revascularisation procedure \[e.g. carotid endarterectomy and/or stent\], mi, coronary artery disease, or peripheral vascular disease) * type 2 diabetes mellitus (t2dm) (diagnosed at least 180 days prior to screening, with glycated haemoglobin \[hba1c\] ≥6.5% (48 mmol/mol) and \<10% (86 mmol/mol) as measured by the central laboratory at screening) * history of at least one self-reported unsuccessful dietary effort to lose body weight further inclusion criteria apply. key exclusion criteria: * current or history of significant alcohol consumption (defined as intake of \>210 g/week in men and \>140 g/week in women on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on the investigator's judgement within the last 5 years. * intake of medications associated with liver injury, hepatic steatosis or steatohepatitis. * history of other chronic liver diseases (e.g. viral hepatitis, autoimmune liver disease, primary biliary cholangitis , primary sclerosing cholangitis, wilson's disease, hemochromatosis, alpha-1 antitrypsin (a1at) deficiency, history of liver transplantation). hepatitis b and c testing will be done at visit 1. participants with positive hepatitis b surface antigen (hbsag) should be excluded. participants treated for hepatitis c must have a negative ribonucleic acid (rna) test at screening and also be hepatitis c virus (hcv) rna negative for at least 3 years prior to screening in order to be eligible for the trial. trial participants with positive hcv antibody and no history of hcv treatment require a negative hcv rna test at screening to be eligible for the trial. * cirrhosis based on clinical assessment, abdominal imaging, liver histology or non-invasive tests assessed at screening (enhanced liver fibrosis (elf) ≥11.3 or fibrosis (fib)-4 ≥3.48 or fibroscan® vcte™ ≥20 kpa or mre ≥4.68 kpa) or a history of cirrhosis. * current decompensated liver disease or previous hepatic decompensation (ascites, spontaneous bacterial peritonitis, portal hypertension bleeding, hepatic encephalopathy, hepatorenal syndrome). * evidence of portal hypertension (e.g. splenomegaly, oesophageal varices, or other portosystemic collateral pathways). further exclusion criteria apply.