A Study to Test Whether BI 685509 Helps People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) Who Had Bleeding in the Esophagus or Fluid Accumulation in the Belly

Study Overview
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Brief Summary
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This study is open to adults with advanced liver cirrhosis caused by hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis or other causes. People can join the study if they have high blood pressure in the portal vein (main vessel going to the liver) and bleeding in the esophagus or fluid accumulation in the belly. The purpose of this study is to find out whether a medicine called BI 685509 helps people with this condition. Participants are put into 2 groups by chance. One group takes BI 685509 tablets and the other group takes placebo tablets. Placebo tablets look like BI 685509 tablets but do not contain any medicine. Participants take a tablet twice a day for 8 weeks. Participants are in the study for 2 to 3 months. During this time, they visit the study site regularly. At 2 of the visits, the doctors check the pressure in the liver vein by inserting a catheter (a long thin tube) that gives information about pressure in the portal vein. The change in blood pressure is then compared between the 2 groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Official Title
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Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Investigate the Effects of One Dose (Up-titration to a Fixed Dose Regimen) of Oral BI 685509 on Portal Hypertension After 8 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Decompensated Cirrhosis After Their First Decompensation Event, Who Are Stabilized CTP 5-7

Conditions
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Hypertension, Portal, Liver Cirrhosis

Intervention / Treatment
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* Drug: Placebo
* Drug: BI 685509


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial 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 (Visit 1a) Diagnosis of cirrhosis due to non-cholestatic liver disease (including Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Non-Alcoholic Steatohepatitis (NASH), alcohol-related liver disease, autoimmune hepatitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency) One previous clinically significant decompensation event with clinical resolution at least 4 weeks prior start of screening (visit 1a): First variceal haemorrhage First episode of clinically significant ascites (requiring intervention in lifestyle [fluid and salt restriction] or medical treatment) Willing and able to undergo Hepatic Venous Pressure Gradient (HVPG) measurements per protocol (based on Investigator judgement) If receiving statins 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 treatment with Non-Selective Beta-Blocker (NSBBs) or carvedilol must be on a stable dose for at least 1 month prior to screening (Visit 1b), with no planned dose change throughout the trial For patient with alcohol-related cirrhosis, abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening (Visit 1a), and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement) Further inclusion criteria apply Exclusion Criteria: History of cholestatic chronic liver disease (e.g. primary biliary cholangitis, primary sclerosing cholangitis) Trial participants without adequate treatment for HBV, HCV or NASH as per local guidance (e.g. antiviral therapy for chronic HBV or HCV infection or lifestyle modification in NASH) If received curative anti-viral therapy for Hepatitis C Virus (HCV), Sustained Virological Response (SVR) sustained for less than 1 years prior to screening If receiving anti-viral therapy for HBV, less than 6 months on a stable dose prior to screening, with planned dose change during the trial or HBV DNA detectable Weight change ≥5% within 6 months prior screening in patients with NASH Must take, or wishes to continue the intake of, restricted concomitant therapy or any concomitant therapy considered likely (based on Investigator judgement) to interfere with the safe conduct of the trial Systolic Blood Pressure (SBP) <100 mmHg or Diastolic Blood Pressure (DBP) <70 mmHg at screening (Visit 1a) Hepatic impairment defined as a Child-Turcotte-Pugh score ≥8 at screening Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br> | Drug: Placebo<br>* Placebo matching BI 685509<br>|
| Experimental: BI 685509<br>This trial contemplates a dose-titration period, depending on dose tolerability. | Drug: BI 685509<br>* BI 685509<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in HVPG from baseline measured after 8 weeks of treatment | Hepatic Venous Pressure Gradient (HVPG) measured in mmHg | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of a response, which is defined as > 10% reduction from baseline HVPG after 8 weeks of treatment | HVPG measured in mmHg | Up to 8 weeks | 
| Occurrence of further decompensation events (i.e. ascites, variceal haemorrhage (VH), and / or overt hepatic encephalopathy (HE)) during the 8 week treatment period |  | Up to 8 weeks | 
| Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8 week treatment period | Common Terminology Criteria for Adverse Events (CTCAE) | Up to 8 weeks | 
| Occurrence of discontinuation due to hypotension or syncope during the 8 week treatment period |  | Up to 8 weeks |