A Study to Test Whether BI 685509 Alone or in Combination With Empagliflozin Helps People With Liver Cirrhosis Caused by Viral Hepatitis or Non-alcoholic Steatohepatitis (NASH) Who Have High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver)

NCT05282121 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 1366-00292021-005171-402023-504257-12-00
• Study Type: interventional
• Target: 90
• Locations: 16 countries
• Sites: 31

Brief Summary

This study is open to adults with liver cirrhosis caused by hepatitis B, hepatitis C or nonalcoholic steatohepatitis (NASH). People can join this study if they have 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 (BI 685509) taken alone or in combination with a medicine called empagliflozin helps people with this condition. Participants take Avenciguat (BI 685509) as tablets twice a day for 8 weeks. Half of the participants with NASH who also have type 2 diabetes take empagliflozin as tablets once a day in addition to Avenciguat (BI 685509). Participants are in the study for about 3 months. During this time, they visit the study site about 10 times. At 2 of the visits, the doctors check the pressure in a liver vein to see whether the treatment works. This is done with a catheter (a long thin tube) and gives information about the pressure in the portal vein. The doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

Liver Diseases; Hypertension, Portal

Outcome Measures

Primary Outcomes (1)

• Percentage Change in HVPG From Baseline (Measured in mmHg) After 8 Weeks of Treatment

  Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in millimetre of mercury \[mmHg\]) after 8 weeks of treatment is reported. Adjusted mean (Least Square Mean) was calculated using an analysis of covariance (ANCOVA) model without imputing the missing data. The model included treatment as fixed classification effects, and baseline HVPG as a linear covariate. The random error was assumed to be normally distributed with mean 0 and variance σ².

  Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Secondary Outcomes (4)

• Occurrence of a Response, Which is Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment

  Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

• Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 8-week Treatment Period

  From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

• Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 8-week Treatment Period

  From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

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

  From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Study Arms (4)

Patients with HBV - avenciguat

EXPERIMENTAL

Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.

Drug: Avenciguat

Patients with HCV - avenciguat

EXPERIMENTAL

Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.

Drug: Avenciguat

Patients with NASH with or without T2DM - avenciguat

EXPERIMENTAL

Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.

Drug: Avenciguat

Patients with NASH with T2DM - avenciguat + empagliflozin

EXPERIMENTAL

Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.

Drug: Avenciguat; Drug: Empagliflozin

Interventions

Avenciguat DRUG

one film-coated tablet orally twice a day, at least 10 hours apart. The starting dose (1 mg) was up-titrated up to 3 mg

Also known as: BI 685509

Patients with HBV - avenciguat; Patients with HCV - avenciguat; Patients with NASH with T2DM - avenciguat + empagliflozin; Patients with NASH with or without T2DM - avenciguat

Empagliflozin DRUG

one 10 mg film-coated tablet of orally once a day

Patients with NASH with T2DM - avenciguat + empagliflozin

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 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)
• 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 (Visit 1b) or within 6 months prior to screening (Visit 1b).
• documented endoscopic proof of oesophageal varices and / or gastric varices at screening (Visit 1b) or within 6 months prior to screening (Visit 1b)
• documented endoscopic-treated oesophageal varices as preventative treatment
• CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) ≥ 10 mmHg (measured at Visit 1c), based on a local interpretation of the pressure tracing
• Diagnosis of compensated cirrhosis due to Hepatitis C virus (HCV), Hepatitis B virus (HBV), or Non-Alcoholic Steatohepatitis (NASH) with or without Type 2 Diabetes Melitus (T2DM). Diagnosis of cirrhosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count \< 150 x 109/L \[150 x 103/microlitre (μL)\], nodular liver surface on imaging or splenomegaly etc.) Diagnosis of NASH based on either i. Current or historic histological diagnosis of NASH OR steatosis OR ii. Clinical diagnosis of NASH based on historic or current imaging diagnosis of fatty liver (Fibroscan, Ultrasound (US), Magnetic Resonance Imaging (MRI), Computed Tomography (CT)) AND at least 2 current or historic comorbidities of the metabolic syndrome (overweight/obesity, T2DM, hypertension, hyperlipidemia)
• Willing and able to undergo 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 months prior to screening (Visit 1b), with no planned dose change throughout the trial

You may not qualify if:

• Previous clinically significant decompensation events (e.g. ascites \[more than perihepatic ascites\], Variceal Haemorrhage (VH) and / or overt / apparent Hepatic Encephalopathy (HE))
• History of other forms of chronic liver disease (e.g. alcohol-related liver disease (ARLD), autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin \[A1At\] deficiency)
• Patients 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 HCV, no sustained virological response (SVR) or SVR sustained for less than 2 years prior to screening or if HCV Ribonucleic Acid (RNA) detectable
• 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 deoxyribonucleic acid (DNA) detectable
• Weight change ≥ 5% within 6 months prior screening
• 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 and Diastolic Blood Pressure (DBP) \< 70 mmHg at screening (Visit 1a)
• Model of End-stage Liver Disease (MELD) score of \> 15 at screening (Visit 1a), calculated by the central laboratory
• Hepatic impairment defined as a Child-Turcotte-Pugh score ≥ B8 at screening (Visit 1a), calculated by the site, using central laboratory results
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \> 5 times upper limit of normal (ULN) at screening (Visit 1a), measured by the central laboratory

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (31)

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Floridian Clinical Research-Miami Lakes-68368

Miami Lakes, Florida, 33016, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Hospital Britanico de Buenos Aires

CABA, 1280AEB, Argentina

Location

Hospital Italiano de Buenos Aires

CABA, C1199ABB, Argentina

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Edegem - UNIV UZ Antwerpen

Edegem, 2650, Belgium

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

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, 310015, China

Location

Zhongshan Hospital Affiliated to Fudan University

Shanghai, 200032, China

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

HOP Beaujon

Clichy, 92118, France

Location

HOP Rangueil

Toulouse, 31059, France

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Western Galilee Hospital

Nahariya, 2210001, Israel

Location

Ospedale Civile di Baggiovara

Baggiovara (MO), 41126, Italy

Location

Azienda Ospedaliera Policlinico di Modena

Modena, 41124, Italy

Location

Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

National Hospital Organization Yokohama Medical Center

Kanagawa, Yokohama, 245-8575, Japan

Location

Osaka Metropolitan University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Amsterdam UMC, location VUMC

Amsterdam, 1105 AZ, Netherlands

Location

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

Cluj-Napoca, 400000, Romania

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Related Publications (1)

• 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.

  PMID: 37095557 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Liver Diseases; Hypertension, Portal

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Digestive System Diseases

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: March 16, 2022
• Study Start: June 28, 2022
• Primary Completion: April 23, 2024
• Study Completion: June 7, 2024
• Last Updated: September 4, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-09

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

RO (1); NL (1); CA (1); JP (2); CN (4); DK (1); BE (1); SG (1); FR (2); ES (2); US (4); AU (1); DE (3); IL (2); AR (2); IT (3)