A Study to Test Whether Two Different Doses of BI 685509 Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver)

Study Overview
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Brief Summary
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This study is open to adults with liver cirrhosis and high blood pressure in the portal vein (main vessel going to the liver). The purpose of this study is to find out whether a medicine called BI 685509 helps people with this condition. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of BI 685509 as tablets twice a day. Participants in the placebo group take placebo as tablets twice a day. Placebo tablets look like BI 685509 tablets but do not contain any medicine. Participants are in the study for about 8 months. During this time, they visit the study site about 14 times. At 3 of the visits, the doctors check the pressure in a liver vein. This is done with a catheter (a long thin tube) and gives information about the pressure in the portal vein. The change in blood pressure is then compared between the 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 Two Doses (Up-titration to a Fixed Dose Regimen) of Oral BI 685509 on Portal Hypertension After 24 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Compensated Cirrhosis

Conditions
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Hypertension, Portal

Intervention / Treatment
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* Drug: BI 685509
* Drug: Placebo matching 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 on 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 Clinical signs of Clinically Significant Portal Hypertension (CSPH) as described by either one of the points below. Each trial patient must have a gastroscopy during the screening period or within 6 months prior to screening. documented endoscopic proof of oesophageal varices and / or gastric varices at screening or within 6 months prior to screening documented endoscopic-treated oesophageal varices as preventative treatment CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) ≥ 10 mmHg, based on a local interpretation of the pressure tracing Diagnosis of compensated alcohol-related cirrhosis. Diagnosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count < 150 x 10^9/L [150 x 10^3/µL], nodular liver surface on imaging or splenomegaly) Abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening, and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement) Willing and able to undergo 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, with no planned dose change throughout the trial Further inclusion criteria apply. Exclusion Criteria: Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic Encephalopathy (HE)) History of other forms of chronic liver disease (e.g. non-alcoholic steatohepatitis (NASH), Hepatitis B virus (HBV), untreated Hepatitis C Virus (HCV), autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency) Has received curative anti-viral therapy with direct-acting anti-virals within the last 2 years for HCV, or, if such treatment was > 2 years ago and there is no sustained virological response (SVR) at screening, or, must take curative anti-viral therapy with direct-acting anti-virals throughout the trial Alcohol-Related Liver Disease (ARLD) without adequate treatment (e.g. lifestyle modification) or with ongoing pathological drinking behaviour (misuse / abuse based on Investigator judgement) 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 and Diastolic Blood Pressure (DBP) < 70 mmHg at screening Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by the central laboratory Hepatic impairment defined as a Child-Turcotte-Pugh score ≥ B8 at screening, calculated by the site, using central laboratory results 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 685509, dose group 1<br> | Drug: BI 685509<br>* BI 685509<br>|
| Experimental: BI 685509, dose group 2<br> | Drug: BI 685509<br>* BI 685509<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo matching BI 685509<br>* Placebo matching BI 685509<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatment |  | at baseline, at week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment |  | at baseline, at week 8 | 
| Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment |  | at baseline, at week 8 | 
| Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment |  | at baseline, at week 24 | 
| Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage (VH), and/or overt Hepatic Encephalopathy (HE)) during the 24 week treatment period |  | up to 24 weeks | 
| Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment period |  | up to 8 weeks | 
| Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment period |  | up to 24 weeks | 
| Occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment period |  | up to 8 weeks | 
| Occurrence of discontinuation due to hypotension or syncope during the 24 week treatment period |  | up to 24 weeks |