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

NCT06082843 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1366-00552023-506083-13-00
• Study Type: interventional
• Target: 22
• Locations: 10 countries
• Sites: 15

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.

Conditions

Hypertension, Portal; Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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 Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week 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

  Up to 46 days.

• Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period

  Up to 46 days.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Avenciguat

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo-matching Avenciguat

Placebo

Avenciguat DRUG

1 millligram (mg), 2 mg, or 3 mg film-coated tablet

Also known as: BI 685509

Avenciguat

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (15)

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

Beijing Friendship Hospital

Beijing, 100050, China

Location

NanFang Hosptial

Guangzhou, 510515, China

Location

HOP Beaujon

Clichy, 92118, France

Location

HOP Rangueil

Toulouse, 31059, France

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Shin-yurigaoka General Hospital

Kanagawa, Kawasaki, 215-0026, Japan

Location

Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"

Cluj-Napoca, 400162, Romania

Location

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggi-do, 14584, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Hypertension, Portal; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: October 13, 2023
• Study Start: January 3, 2024
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

AU (1); FR (2); US (2); DE (2); CA (1); RO (1); KR (1); JP (1); ES (2); CN (2)