Resumen

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 Avenciguat helps people with this condition. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of Avenciguat as tablets twice a day. Participants in the placebo group take placebo as tablets twice a day. Placebo tablets look like Avenciguat 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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

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)

Criterios de exclusión

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

Intervenciones

drug

Avenciguat (BI 685509)

Participants received Avenciguat twice daily (BID) throughout the study. Up-titration depended on the assigned dose group. At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet. At Visit 3 (Week 2), the dose was increased to one 2 mg Avenciguat tablet per dose. From Visit 4 onward (Week 3+), participants received one 3 mg Avenciguat tablet per dose. This regimen continued for 24 weeks, with all doses taken with water, with or without food.

drug

Placebo matching Avenciguat (BI 685509)

Participants received matching placebo twice daily (BID) throughout the study. At Visit 2 (Week 1), each dose included one 1 mg and one 2 mg placebo tablet (four tablets daily). A pseudo up-titration was applied at Visit 3 (Week 2), maintaining the same tablet composition to preserve blinding. From Visit 4 (Week 3) onward, a second pseudo up-titration adjusted each dose to one 2 mg and one 3 mg placebo tablet (four tablets daily). All doses were taken with water, with or without food.