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

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

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.

Study Overview

• Status: Terminated
• Conditions: Liver Cirrhosis; Hypertension, Portal
• Intervention / Treatment: Drug: Placebo; Drug: Avenciguat

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • AKH - Medical University of Vienna
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• China
  • Beijing, China, 100050
    • Beijing Friendship Hospital
  • Guangzhou, China, 510515
    • NanFang Hosptial
• France
  • Clichy, France, 92118
    • HOP Beaujon
  • Toulouse, France, 31059
    • HOP Rangueil
• Germany
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
• Japan
  • Kanagawa, Kawasaki, Japan, 215-0026
    • Shin-yurigaoka General Hospital
• Korea, Republic of
  • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14584
    • Soon Chun Hyang University Hospital Bucheon
• Romania
  • Cluj-Napoca, Romania, 400162
    • Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
• United States
  • California
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Placebo-matching Avenciguat
Experimental: 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.	Drug: Avenciguat; 1 millligram (mg), 2 mg, or 3 mg film-coated tablet; Other Names: BI 685509

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of a Response, Defined as >10% Reduction From Baseline Hepatic Venous Pressure Gradient (HVPG) (Measured in mmHg) After 8 Weeks of Treatment	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.	At baseline and at Week 8.
Occurrence of Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week Treatment Period	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.	Up to 46 days.
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement During the 8-week Treatment Period	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.	Up to 46 days.
Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period	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.	Up to 46 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: October 9, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Digestive System Diseases; Liver Diseases; Hypertension; Fibrosis; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: 1366-0055; 2023-506083-13-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once the criteria in section 'time frame frame' are fulfilled , researchers can use the following link https:// www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
• IPD Sharing Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents upon signing of a 'Document Sharing Agreement'.For study data 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No