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)

NCT ID: NCT05282121

Last Updated: 2025-09-04

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-28

Study Completion Date

2024-06-07

Brief Summary

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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.

Detailed Description

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Conditions

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Liver Diseases Hypertension, Portal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Patients with HBV - avenciguat

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.

Group Type EXPERIMENTAL

Avenciguat

Intervention Type 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

Patients with HCV - avenciguat

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.

Group Type EXPERIMENTAL

Avenciguat

Intervention Type 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

Patients with NASH with or without T2DM - avenciguat

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.

Group Type EXPERIMENTAL

Avenciguat

Intervention Type 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

Patients with NASH with T2DM - avenciguat + empagliflozin

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.

Group Type EXPERIMENTAL

Avenciguat

Intervention Type 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

Empagliflozin

Intervention Type DRUG

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

Interventions

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Avenciguat

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

Intervention Type DRUG

Empagliflozin

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

Intervention Type DRUG

Other Intervention Names

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BI 685509

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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California Liver Research Institute

Pasadena, California, United States

Site Status

Inland Empire Clinical Trials, LLC

Rialto, California, United States

Site Status

Floridian Clinical Research-Miami Lakes-68368

Miami Lakes, Florida, United States

Site Status

American Research Corporation

San Antonio, Texas, United States

Site Status

Hospital Britanico de Buenos Aires

CABA, , Argentina

Site Status

Hospital Italiano de Buenos Aires

CABA, , Argentina

Site Status

AKH - Medical University of Vienna

Vienna, , Austria

Site Status

Edegem - UNIV UZ Antwerpen

Edegem, , Belgium

Site Status

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Site Status

Beijing Friendship Hospital

Beijing, , China

Site Status

NanFang Hosptial

Guangzhou, , China

Site Status

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, , China

Site Status

Zhongshan Hospital Affiliated to Fudan University

Shanghai, , China

Site Status

Hvidovre Hospital

Hvidovre, , Denmark

Site Status

HOP Beaujon

Clichy, , France

Site Status

HOP Rangueil

Toulouse, , France

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Site Status

Universitätsklinikum Münster

Münster, , Germany

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Western Galilee Hospital

Nahariya, , Israel

Site Status

Ospedale Civile di Baggiovara

Baggiovara (MO), , Italy

Site Status

Azienda Ospedaliera Policlinico di Modena

Modena, , Italy

Site Status

Policlinico "Paolo Giaccone"

Palermo, , Italy

Site Status

National Hospital Organization Yokohama Medical Center

Kanagawa, Yokohama, , Japan

Site Status

Osaka Metropolitan University Hospital

Osaka, Osaka, , Japan

Site Status

Amsterdam UMC, location VUMC

Amsterdam, , Netherlands

Site Status

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

Cluj-Napoca, , Romania

Site Status

Singapore General Hospital

Singapore, , Singapore

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Countries

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United States Argentina Austria Belgium Canada China Denmark France Germany Israel Italy Japan Netherlands Romania Singapore Spain

References

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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

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2021-005171-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-504257-12-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

1366-0029

Identifier Type: -

Identifier Source: org_study_id

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