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A study to test whether BI 685509 alone or in combination with empagliflozin helps people with liver cirrhosis caused by viral hepatitis or non-alcoholic steatohepatitis (NASH) who have high blood pressure in the portal vein (main vessel going to the liver)

Phase 2
Recruiting
Conditions
Patients with CSPH in compensated cirrhosis due to HBV, HCV, and NASH with or without T2DM
Registration Number
JPRN-jRCT2031220376
Lead Sponsor
Kutsunai Mitsuru
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
5
Inclusion Criteria

Male or female who is >= 18 (or who is of legal age in countries where that is greater than 18) and <= 75 years old at screening (Visit1a)
Clinical signs of CSPH as described by either one of the points below:
a) documented endoscopic proof of oesophageal varices and / or gastric varices at screening (Visit 1b) or within 3 months prior to screening (Visit 1b)
b) documented endoscopic-treated oesophageal varices as preventative treatment
CSPH defined as baseline HVPG >= 10 mmHg (measured at Visit 1c), based on a local interpretation of the pressure tracing
Diagnosis of compensated cirrhosis due to HBV, HCV or NASH with or without T2DM. Diagnosis of cirrhosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count < 150 x 109/L [150 x103/micro L], nodular liver surface on imaging or splenomegaly etc.)
Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement)
If receiving statins, NSBBs or carvedilol must be on a stable dose for at least 3 months prior to screening (Visit 1b), with no planned dose change throughout the trial
If receiving pioglitazone, GLP1-agonists, or vitamin E must be on a stable dose for at least 3 months prior to screening (Visit1b), with no planned dose change throughout the trial

Exclusion Criteria

Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], VH and / or apparent HE)
History of other forms of chronic liver disease (e.g. alcoholrelated liver disease, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, haemachromatosis, alpha-1 antitrypsin [A1At] deficiency)
Patients without adequate treatment for HBV, HCV, or NASH (e.g. antiviral therapy in chronic HBV or HCV or lifestyle modification in NASH)
SBP < 100 mmHg and DBP < 70 mmHg at screening (Visit 1a)
Model of End-stage Liver Disease (MELD) score of more than 15 at screening (Visit 1a)
Hepatic impairment defined as a Child-Turcotte-Pugh score >= B8 at screening (Visit 1a)
ALT or AST > 5 times upper limit of normal (ULN) at screening (Visit 1a)
eGFR (CKD-EPI formula) < 20 mL/min/1.73 m2 at screening (Visit 1a)
Alpha-fetoprotein > 50 ng/mL (> 50 micro g/L) at screening (Visit 1a)
History of clinically relevant orthostatic hypotension, faintingspells or blackouts due to hypotension or of unknown origin (based on Investigator judgement)
Current or planned SGLT2i / SGLT-1/2i treatment
Type 1 Diabetes Mellitus

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment.
Secondary Outcome Measures
NameTimeMethod
Occurrence of a response, which is defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment<br>Occurrence of one or more decompensation events (i.e. ascites, variceal haemorrhage [VH], and / or overt hepatic encephalopathy [HE]) during the 8 week treatment period<br>Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8 week treatment period<br>Occurrence of discontinuation due to hypotension or syncope during the 8 week treatment period
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