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 Liver)

NCT ID: NCT05161481

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-27
• Study Completion Date: 2024-06-12

Brief Summary

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.

Conditions

Hypertension, Portal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Avenciguat 2 mg BID

Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.

Group Type: EXPERIMENTAL

Avenciguat (BI 685509)

Intervention Type: DRUG

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.

Avenciguat 3 mg BID

Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.

Group Type: EXPERIMENTAL

Avenciguat (BI 685509)

Intervention Type: DRUG

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.

Placebo

Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.

Group Type: PLACEBO_COMPARATOR

Placebo matching Avenciguat (BI 685509)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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)

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

California Liver Research Institute

Pasadena, California, United States

Inland Empire Clinical Trials, LLC

Rialto, California, United States

Floridian Clinical Research-Miami Lakes-68368

Miami Lakes, Florida, United States

Northwell Health Center for Liver Disease

Manhasset, New York, United States

Medical University of South Carolina

Charleston, South Carolina, United States

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, United States

Hospital Italiano de Buenos Aires

CABA, , Argentina

Medical University of Innsbruck

Innsbruck, , Austria

AKH - Medical University of Vienna

Vienna, , Austria

Edegem - UNIV UZ Antwerpen

Edegem, , Belgium

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Beijing Friendship Hospital

Beijing, , China

Beijing Youan Hospital, Capital Medical University

Beijing, , China

NanFang Hosptial

Guangzhou, , China

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, , China

University Hospital Dubrava

Zagreb, , Croatia

Hvidovre Hospital

Hvidovre, , Denmark

HOP d'Angers

Angers, , France

HOP Rangueil

Toulouse, , France

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Universitätsklinikum Münster

Münster, , Germany

St. Josefs-Hospital, Wiesbaden

Wiesbaden, , Germany

Western Galilee Hospital

Nahariya, , Israel

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliera Policlinico di Modena

Modena, , Italy

Policlinico "Paolo Giaccone"

Palermo, , Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, , Italy

Shin-yurigaoka General Hospital

Kanagawa, Kawasaki, , Japan

Kitasato University Hospital

Kanagawa, Sagamihara, , Japan

Yokohama City University Hospital

Kanagawa, Yokohama, , Japan

National Hospital Organization Yokohama Medical Center

Kanagawa, Yokohama, , Japan

Osaka Metropolitan University Hospital

Osaka, Osaka, , Japan

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

ULS de Santa Maria, E.P.E

Lisbon, , Portugal

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

Cluj-Napoca, , Romania

Singapore General Hospital

Singapore, , Singapore

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggi-do, , South Korea

Yonsei University Wonju Severance Christian Hospital

Wonju-si, Gangwon State, , South Korea

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Puerta de Hierro

Majadahonda, , Spain

Ospedale Regionale di Lugano

Viganello, , Switzerland

Taipei Veterans General Hospital

Taipei, , Taiwan

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

St Mary's Hospital

London, , United Kingdom

Countries

United States; Argentina; Austria; Belgium; Canada; China; Croatia; Denmark; France; Germany; Israel; Italy; Japan; Netherlands; Portugal; Romania; Singapore; South Korea; Spain; Switzerland; Taiwan; United Kingdom

References

Reiberger T, Berzigotti A, Trebicka J, Ertle J, Gashaw I, Swallow R, Tomisser A. The rationale and study design of two phase II trials examining the effects of BI 685,509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis. Trials. 2023 Apr 24;24(1):293. doi: 10.1186/s13063-023-07291-3.

Reference Type: DERIVED

PMID: 37095557 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2021-001285-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1366-0021

Identifier Type: -

Identifier Source: org_study_id