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A Phase III double-blind, randomised, placebo-controlled trial to evaluate liver-related clinical outcomes and safety of once weekly injected survodutide in participants with compensated non-alcoholic steatohepatitis/metabolic dysfunction associated steatohepatitis (NASH/MASH) cirrhosis

A study to test whether survodutide helps people with a liver disease called NASH/MASH who have cirrhosis

Popp Marcus

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Str. 173 Ingelheim 55216, Germany

marcus.popp@boehringer-ingelheim.com

Rosario Chikako

Parexel International Inc.

Kayabacho Tower, 1-21-2, Shinkawa, Chuo-ku, Tokyo

+81-80-8929-3137

Clinicaltrial-registration@parexel.com

Recruiting

Dec. 16, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Male or female adults >=18 years of age at the time of screening, and at least the legal age of consent in countries where it is >18 years
2. BMI >=27 kg/m2(>=25 kg/m2 for Asian trial participants)
3. Compensated MASH cirrhosis diagnosed according to modified Liver Forum criteria (Noureddin et al, Gastroenterology 2020;159:422-427).
4. MRI-PDFF fat fraction >=5% or FibroScan with CAP >=288 dB/m, obtained during the screening period or a historic MRI-PDFF or FibroScan with CAP <=12 weeks prior to randomisation (except for patients with "cryptogenic cirrhosis" where MRI-PDFF <5% or FibroScan with CAP < 288 dB/m is allowed). This inclusion criterion does not apply for participants with a recent (<=12 months prior to randomisation) liver biopsy showing steatosis/steatohepatitis.
Further inclusion criteria apply

Liver related
1. Current or history (<5 years) of significant alcohol consumption, defined as an average of > 140 g/week in female patients and >210 g/week in male patients, for a period of >3 consecutive months, or an inability to reliably quantify alcohol consumption based upon judgment of the investigator.
2. MELD score >12 due to liver disease
3. History or current (i.e. at screening) hepatic decompensation event defined as presence of any of the following but not limited to:
- History of portal hypertension-related upper GI bleeding
- Ascites
- HE >=Grade 1 according to the West Haven criteria [
4. Any of the following lab test result at screening:
- Albumin below <3.5 g/dL (<35.0 g/L)
- INR >1.3 unless due to therapeutic anticoagulants
- TBL >1.2x ULN
NOTE: Trial participants with Gilbert Syndrome are eligible with a TBL >1.2x upper limit of normal (ULN) if reticulocyte count is within normal limits, haemoglobin is within normal limits unless due to chronic anaemia and unrelated to haemolysis, and direct bilirubin is <20% of TBL.
- Alkaline phosphatase >1.5x ULN
- Platelet count <100,000/uL (<100 GI/L)
5. History or evidence of other chronic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis or overlap syndrome, Wilson's disease, alpha-1-antitrypsin deficiency, or genetic haemochromatosis
6. Hepatitis B positive (defined as positive HBsAg)
7. Hepatitis C positive (defined as positive HCV antibody and a positive HCV RNA).
8. Evidence of alcoholic liver disease, or drug-induced liver disease, as defined on the basis of typical exposure and history
9. Serum AST and/or ALT >5x ULN
10. History of liver transplantation or listed for liver transplantation
11. History of TIPS or other radiological/surgical procedure for portal hypertension treatment
Further exclusion criteria apply

Both

Compensated non-alcoholic steatohepatitis/metabolic dysfunction associated steatohepatitis (NASH/MAS

Subcutaneous maintenance doses once weekly

Time to first occurrence of any component of the composite clinical endpoint (at EoS) consisting of:
- All-cause mortality
- Liver transplant
- Hepatic decompensation events
- Worsening of MELD score to >=15
- Progression to CSPH

At Week 76:
- Absolute change from baseline in ELF score
- Percentage change from baseline in body weight
- Absolute change from baseline in HbA1c in participants with T2DM at baseline (%)
- Absolute change from baseline in liver stiffness in FibroScan VCTE (kPa)
- Percentage change from baseline in liver stiffness in FibroScan VCTE
At EoS:
- Time to first occurrence of progression to CSPH
- Time to first occurrence of any of the hepatic decompensation events (ascites, HE, or portal hypertension-related upper GI bleeding), or worsening of MELD score to >=15
- Occurrence of all-cause hospitalisation (first and recurrent)
- Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE)
At Week 76
- Absolute changes from baseline in lipids (mg/dL)
- Absolute change from baseline in AST (U/L)
- Absolute change from baseline in ALT (U/L)
- Absolute change from baseline in liver stiffness assesses by MRE

+81-3-3881-6116

Yes

Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

Argentina/Australia/Brazil/Canada/Chile/China/Georgia/Hong Kong/Jordan/Kazakhstan/New Zealand/Saudi Arabia/Singapore/South Africa/Switzerland/Taiwan/Turkey/United Kingdom/South Korea/Mexico/India/USA/Austria/Belgium/Bulgaria/Czech Republic/Germany/Hungary/Italy/Netherlands