Overview
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 13 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
Key inclusion criteria:
- Male or female, 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] ≥160 mg/dL [≥4.1 mmol/L] or triglycerides ≥150 mg/dL [≥1.7 mmol/L], or high-density lipoprotein (HDL] <40 mg/dL (<1.0 mmol/L] for men or HDL<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) 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.
- 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)
- 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.