A Study to Test Whether Avenciguat 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

Phase 2

Terminated

Conditions: Hypertension, Portal
Liver Cirrhosis

Interventions: Drug: Placebo
Drug: Avenciguat

Registration Number: NCT06082843

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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 avenciguat helps people with this condition.

Participants are put into 2 groups by chance. One group takes avenciguat tablets and the other group takes placebo tablets. Placebo tablets look like avenciguat 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 22

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of placebo-matching avenciguat (BI 685509) orally twice daily (bid). Participants started the treatment with a 1 mg film-coated tablet of placebo-matching avenciguat administered bid. One week later (Visit 3), the dosage was increased to 2 mg film-coated tablets bid, and after another week, participants started on 3 mg film-coated tablet bid (Visit 4), which was maintained for the rest of the treatment.
Avenciguat	Avenciguat	Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of avenciguat (BI 685509) orally twice daily (bid), up to a total dose of 6 milligrams (mg). The treatment period began (Visit 2) with a 1 mg film-coated tablet of avenciguat administered bid. If the dose was well-tolerated, it was increased to 2 mg film-coated tablets bid after one week (Visit 3), followed by an increase to the maintenance dose of 3 mg film-coated tablet one week later (Visit 4). If the maintenance dose of avenciguat was not well-tolerated, it was reduced, with the participants remaining on the highest tolerated dose for the rest of the treatment period.

Primary Outcome Measures

Name	Time	Method
Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline (Measured in mmHg) After 8 Weeks of Treatment	At baseline and at Week 8.	Percentage change in hepatic venous pressure gradient (HVPG) from baseline to Week 8.

Secondary Outcome Measures

Name	Time	Method
Occurrence of a Response, Defined as >10% Reduction From Baseline Hepatic Venous Pressure Gradient (HVPG) (Measured in mmHg) After 8 Weeks of Treatment	At baseline and at Week 8.	Occurrence of a response, defined as at least a 10% reduction in the hepatic venous pressure gradient (HVPG) (measured in mmHg) after 8 weeks of treatment.
Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period	Up to 46 days.	Number of participants that discontinued avenciguat due to hypotension or syncope. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period.
Occurrence of Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week Treatment Period	Up to 46 days.	Number of participants with at least one decompensation events. Ascites, variceal hemorrhage (VH), and hepatic encephalopathy were defined as further decompensations events. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period.
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement During the 8-week Treatment Period	Up to 46 days.	Number of participants with grade 3 or higher common terminology criteria for adverse events (CTCAE) hypotension or syncope base on the investigator judgment. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period.

Trial Locations

Locations (15): California Liver Research Institute
🇺🇸
Pasadena, California, United States
Inland Empire Clinical Trials, LLC
🇺🇸
Rialto, California, United States
AKH - Medical University of Vienna
🇦🇹
Vienna, Austria
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦
Montreal, Quebec, Canada
Beijing Friendship Hospital
🇨🇳
Beijing, China
NanFang Hosptial
🇨🇳
Guangzhou, China
HOP Beaujon
🇫🇷
Clichy, France
HOP Rangueil
🇫🇷
Toulouse, France
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Germany
Universitätsklinikum Münster
🇩🇪
Münster, Germany
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California Liver Research Institute
🇺🇸Pasadena, California, United States