Non-Alcoholic SteatoHepatitis (NASH), Obesity
Conditions
Brief 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.
Interventions
COMBINATION_PRODUCTSurvodutide
Survodutide, pre-filled syringe
COMBINATION_PRODUCTPlacebo
Placebo matching survodutide, pre-filled syringe
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) [%] | at baseline, at week 48 |
| Relative change (%) in body weight [kg] from baseline to Week 48 | at baseline, at week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Absolute change from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%] | at baseline, at week 48 |
| Relative change (%) from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%] | at baseline, at week 48 |
| Reduction from baseline to Week 48 in Iron corrected T1 (cT1) [ms] levels of ≥80 ms (yes/no) | at baseline, at week 48 |
| Absolute change from baseline to Week 48 in alanine amino transferase (ALT) [U/L] levels | at baseline, at week 48 |
| Relative change from baseline to Week 48 in alanine amino transferase (ALT) [U/L] levels | at baseline, at week 48 |
| Absolute change from baseline to Week 48 in waist circumference [cm] | at baseline, at week 48 |
| Relative change from baseline to Week 48 in waist circumference [cm] | at baseline, at week 48 |
| Absolute change from baseline to Week 48 in Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (Fasting Plasma Insulin (FPI) [mlU/L] · Fasting Plasma Glucose (FPG) [mmol/L]/22.5) | at baseline, at week 48 |
| Relative change from baseline to Week 48 in HOMA-IR (FPI [mlU/L] · FPG [mmol/L]/22.5) | at baseline, at week 48 |
| Absolute change from baseline to Week 48 in liver stiffness [kPa] assessed by magnetic resonance elastography (MRE) | at baseline, at week 48 |
| Relative change from baseline to Week 48 in liver stiffness [kPa] assessed by magnetic resonance elastography (MRE) | at baseline, at week 48 |
| Absolute change in liver volume [mL] from baseline to Week 48 measured using MRI | at baseline, at week 48 |
| Relative change in liver volume [mL] from baseline to Week 48 measured using MRI | at baseline, at week 48 |
Countries
Spain, United States
Outcome results
None listed