A Study to Test Whether Two Different Doses of Avenciguat Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Live

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension, Portal
• Intervention / Treatment: Drug: Avenciguat (BI 685509); Drug: Placebo matching Avenciguat (BI 685509)

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• Argentina
  • Caba, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
• Austria
  • Innsbruck, Austria, 6020
    • Medical University of Innsbruck
  • Wien, Austria, 1090
    • AKH - Medical University of Vienna
• Belgium
  • Edegem, Belgium, 2650
    • Edegem - UNIV UZ Antwerpen
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• China
  • Beijing, China, 100050
    • Beijing Friendship Hospital
  • Beijing, China, 100071
    • Beijing Youan Hospital, Capital Medical University
  • Guangzhou, China, 510515
    • NanFang Hosptial
  • Hangzhou, China, 310000
    • The Affiliated Hospital of Hangzhou Normal University
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Dubrava
• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
• France
  • Angers, France, 49933
    • HOP d'Angers
  • Toulouse, France, 31059
    • HOP Rangueil
• Germany
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Wiesbaden, Germany, 65189
    • St. Josefs-Hospital, Wiesbaden
• Israel
  • Nahariya, Israel, 2210001
    • Western Galilee Hospital
• Italy
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41124
    • Azienda Ospedaliera Policlinico di Modena
  • Palermo, Italy, 90127
    • A.O. Univ. Policlinico "Paolo Giaccone"
  • Roma, Italy, 00195
    • Poli Univ A. Gemelli
• Japan
  • Kanagawa, Kawasaki, Japan, 215-0026
    • Shin-yurigaoka General Hospital
  • Kanagawa, Sagamihara, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Yokohama, Japan, 236-0004
    • Yokohama City University Hospital
  • Kanagawa, Yokohama, Japan, 245-8575
    • National Hospital Organization Yokohama Medical Center
  • Osaka, Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
• Korea, Republic of
  • Bucheon, Korea, Republic of, 14584
    • Soon Chun Hyang University Hospital Bucheon
  • Wonju, Korea, Republic of, 26426
    • Yonsei University Wonju Severance Christian Hospital
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
• Portugal
  • Lisboa, Portugal, 1649-035
    • ULS de Santa Maria, E.P.E
• Romania
  • Cluj-Napoca, Romania, 400000
    • Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Majadahonda, Spain, 28222
    • Hospital Puerta de Hierro
• Switzerland
  • Viganello, Switzerland, 6962
    • Ospedale Regionale di Lugano
• Taiwan
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital
• United States
  • California
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials, LLC
  • Florida
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health Center for Liver Disease
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
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

3. 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
4. CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) ≥ 10 mmHg, 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 10^9/L [150 x 10^3/µL], nodular liver surface on imaging or splenomegaly)
6. 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)
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, with no planned dose change throughout the trial Further inclusion criteria apply.

Exclusion Criteria:

1. Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic Encephalopathy (HE))
2. 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)
3. 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
4. Alcohol-Related Liver Disease (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. Systolic Blood Pressure (SBP) < 100 mmHg and Diastolic Blood Pressure (DBP) < 70 mmHg at screening
7. Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by the central laboratory
8. Hepatic impairment defined as a Child-Turcotte-Pugh score ≥ B8 at screening, calculated by the site, using central laboratory results Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo matching Avenciguat (BI 685509); Placebo matching Avenciguat (BI 685509)
Experimental: Avenciguat (BI 685509), dose group 1	Drug: Avenciguat (BI 685509); Avenciguat (BI 685509)
Experimental: Avenciguat (BI 685509), dose group 2	Drug: Avenciguat (BI 685509); Avenciguat (BI 685509)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatment	at baseline, at week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment	at baseline, at week 8
Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment	at baseline, at week 8
Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment	at baseline, at week 24
Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage (VH), and/or overt Hepatic Encephalopathy (HE)) during the 24 week treatment period	up to 24 weeks
Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment period	up to 8 weeks
Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment period	up to 24 weeks
Occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment period	up to 8 weeks
Occurrence of discontinuation due to hypotension or syncope during the 24 week treatment period	up to 24 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2022
• Primary Completion (Estimated): September 26, 2024
• Study Completion (Estimated): October 24, 2024

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hypertension; Hypertension, Portal
• Other Study ID Numbers: 1366-0021; 2021-001285-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Once the time frame criteria given under number 4 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