1404-0044

About this trial

Last updated 7 months ago

Study ID

1404-0044

Status

Recruiting

Type

Interventional

Phase

Phase 3

Placebo

Yes

Accepting

18+ Years

All

Not accepting

Healthy Volunteers

Trial Timing

Started 9 months ago

This study is open to adults who are at least 18 years old 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 visits the liver is measured using different imaging methods. At 2 or 3 visits doctors take a small sample of liver tissue (biopsy). The participants also fill in questionnaires about their symptoms and quality of life. The results are compared between the groups to see whether the treatment works.

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, with at least 1 point in inflammation and ballooning each) and fibrosis stage F2-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomisation

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

5. 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 (unless participant is on anticoagulants)

- OR total serum bilirubin concentration ≥1.5x ULN (participants with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is within normal reference range)

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 (including hepatic encephalopathy, variceal bleeding, ascites, and spontaneous bacterial peritonitis)

8. Model for end-stage liver disease (MELD) score ≥12 due to liver disease.

9. Treatment with any medication for the indication obesity within 3 months before screening biopsy or historical biopsy time point

10. History of either chronic or acute pancreatitis or elevation of serum lipase or amylase >2x ULN as measured by the central laboratory at screening

11. Major surgery (in the opinion of the investigator) performed within 3 months prior to screening or planned during the trial

12. Further exclusion criteria apply

LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Moderate or Advanced Liver Fibrosis