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

1. Signed and dated written informed consent in accordance with ICH-GCP and
local
legislation prior to admission to the trial.
2. 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).
3. Clinical signs of CSPH as described by either one of the points below. Each
trial patient must have a gastroscopy during the screening period (Visit 1b) or
within 6 months prior to screening (Visit 1b).
• documented endoscopic proof of oesophageal varices and / or gastric varices at
screening (Visit 1b) or within 6 months prior to screening (Visit 1b)
• documented endoscopic-treated oesophageal varices as preventative treatment
4. CSPH defined as baseline HVPG >= 10 mmHg (measured at Visit 1c), based on a
local interpretation of the pressure tracing.
5. 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 109/L [150 x 103/µL], nodular liver
surface on imaging or splenomegaly).
6. 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).
7. Willing and able to undergo HVPG measurements per protocol (based on
Investigator judgement)
8. 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.
9. If receiving treatment with 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.
10. WOCBP must be ready and able to use highly effective methods of birth
control per ICH M3 (R2) that result in a low failure rate of less than 1% per
year when used consistently and correctly from the randomisation visit (Visit
2) until 7 days after the last treatment in this trial.
11. Men able to father a child and who have a female sexual partner of CBP,
must use a condom with or without spermicide, or adopt complete sexual
abstinence, or be vasectomised, from the randomisation visit (Visit 2) until 7
days after the last treatment in this trial.

1. Previous clinically significant decompensation events (e.g. ascites [more
than perihepatic ascites], VH and / or apparent HE).
2. History of other forms of chronic liver disease (e.g. non-alcoholic
steatohepatitis [NASH], Hepatitis B virus [HBV], untreated HCV, autoimmune
liver disease, primary biliary cholangitis, primary sclerosing cholangitis,
Wilson*s disease, haemachromatosis, alpha-1 antitrypsin [A1At] deficiency).
3. Has received curative anti-viral therapy with direct-acting anti-virals
within the last 2 years for HCV, or, if such a 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.
4. ARLD without adequate treatment (e.g. lifestyle modification) or with
ongoing pathological drinking behaviour (misuse / abuse based on Investigator
judgement).
5. 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.
6. SBP < 100 mmHg and DBP < 70 mmHg at screening (Visit 1a).
7. Model of End-stage Liver Disease (MELD) score of > 15 at screening (Visit
1a), calculated by the central laboratory.
8. Hepatic impairment defined as a Child-Turcotte-Pugh score >= B8 at screening
(Visit 1a), calculated by the site, using central laboratory results.
9. ALT or AST > 5 times upper limit of normal (ULN) at screening (Visit 1a),
measured by the central laboratory.
10. eGFR (CKD-EPI formula) < 20 mL/min/1.73 m2 at screening (Visit 1a),
measured by the central laboratory.
11. Alpha-fetoprotein > 50 ng/mL (> 50 µg/L) at screening (Visit 1a), measured
by the central laboratory.
12. An active infection with SARS-CoV-2 (or who is known to have a positive
test from screening [Visit 1a] until randomisation [Visit 2]).
13. Prior orthotopic liver transplantation.
14. Prior or planned TIPS or other porto-systemic bypass procedure.
15. Known portal vein thrombosis.
16. History of clinically relevant orthostatic hypotension, fainting spells or
blackouts due to hypotension or of unknown origin (based on Investigator
judgement).
17. Any documented active or suspected malignancy or history of malignancy
within 5 years prior to screening (Visit 1a), except appropriately treated
basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
18. QTcF-interval > 450 ms in men or > 470 ms in women at screening, a family
history of long QT syndrome, or concomitant use of therapies with a known risk
of Torsade de Pointes at screening or planned initiation of such therapies
during the trial.
19. Major surgery (based on Investigator judgement) performed within 3 months
prior to randomisation (Visit 2) or planned during the trial, e.g. hip
replacement.
20. Contraindication to any of the trial assessments (e.g. poor patient
co-operation for gastroscopy, cardiac pacemakers for FibroScan [if
contraindicated based on local market approval] etc.).
21. History of (in the 6 months prior to randomisation [Visit 2]), or ongoing,
chronic drug abuse, or not expected to comply with the protocol requirements
for any other reason that, based on Investigator judgement, makes the patient
an unreliable trial recruit or unlikely to complete the trial as scheduled.
22. Any other medical condition that, based on Investigator judgement, poses a
safety risk for the patient or may interfere with the objectives of the trial.
23. Previous randomisation in this trial, previous exposure to BI 685509, or an
allergy/ contraindication to BI 685509 and matching placebo / or any of their
excipients.
24. Currently enrolled in another investigational device or drug trial, or less
than 30 days or 5 half-lives (whichever is longer) prior to randomisation
(Visit 2) since ending another investigational device or drug trial, or
receiving other investigational treatment(s).
25. Women who are pregnant, nursing, or who plan to become pregnant whilst in
the trial.