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)

Last updated: December 23, 2024
Sponsor: Boehringer Ingelheim
Overall Status: Terminated

Phase

2

Condition

Vascular Diseases

Circulation Disorders

Stress

Treatment

Empagliflozin

BI 685509

Avenciguat (BI 685509)

Clinical Study ID

NCT05282121
1366-0029
2021-005171-40
2023-504257-12-00
2022-500332-11-00
  • Ages 18-75
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Signed and dated written informed consent in accordance with ICH-GCP and locallegislation prior to admission to the trial

  • Male or female who is ≥ 18 (or who is of legal age in countries where that isgreater than 18) and ≤ 75 years old at screening (Visit 1a)

  • Clinical signs of Clinically Significant Portal Hypertension (CSPH) as described byeither one of the points below. Each trial patient must have a gastroscopy duringthe screening period (Visit 1b) or within 6 months prior to screening (Visit 1b).

  • documented endoscopic proof of oesophageal varices and / or gastric varices atscreening (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 (measuredat 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 DiabetesMelitus (T2DM). Diagnosis of cirrhosis must be based on histology (historical datais 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 splenomegalyetc.) Diagnosis of NASH based on either i. Current or historic histologicaldiagnosis of NASH OR steatosis OR ii. Clinical diagnosis of NASH based on historicor current imaging diagnosis of fatty liver (Fibroscan, Ultrasound (US), MagneticResonance Imaging (MRI), Computed Tomography (CT)) AND at least 2 current orhistoric comorbidities of the metabolic syndrome (overweight/obesity, T2DM,hypertension, hyperlipidemia)

  • Willing and able to undergo HVPG measurements per protocol (based on Investigatorjudgement)

  • If receiving statins must be on a stable dose for at least 3 months prior toscreening (Visit 1b), with no planned dose change throughout the trial

  • If receiving treatment with Non-Selective Beta-Blocker (NSBBs) or carvedilol must beon a stable dose for at least 1 months prior to screening (Visit 1b), with noplanned dose change throughout the trial

  • Further inclusion criteria apply

Exclusion

Exclusion Criteria:

  • Previous clinically significant decompensation events (e.g. ascites [more thanperihepatic ascites], Variceal Haemorrhage (VH) and / or overt / apparent HepaticEncephalopathy (HE))

  • History of other forms of chronic liver disease (e.g. alcohol-related liver disease (ARLD), autoimmune liver disease, primary biliary sclerosis, primary sclerosingcholangitis, 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 inNASH)

  • if received curative anti-viral therapy for HCV, no sustained virologicalresponse (SVR) or SVR sustained for less than 2 years prior to screening or ifHCV Ribonucleic Acid (RNA) detectable

  • If receiving anti-viral therapy for HBV, less than 6 months on a stable doseprior to screening, with planned dose change during the trial or HBVdeoxyribonucleic acid (DNA) detectable

  • Weight change ≥ 5% within 6 months prior screening

  • Must take, or wishes to continue the intake of, restricted concomitant therapy orany concomitant therapy considered likely (based on Investigator judgement) tointerfere with the safe conduct of the trial

  • Systolic Blood Pressure (SBP) < 100 mmHg and Diastolic Blood Pressure (DBP) < 70mmHg 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 upperlimit of normal (ULN) at screening (Visit 1a), measured by the central laboratory

  • Further exclusion criteria apply

Study Design

Total Participants: 90
Treatment Group(s): 3
Primary Treatment: Empagliflozin
Phase: 2
Study Start date:
June 28, 2022
Estimated Completion Date:
June 07, 2024

Connect with a study center

  • Hospital Britanico de Buenos Aires

    Caba, 1280AEB
    Argentina

    Site Not Available

  • Hospital Italiano de Buenos Aires

    Caba, C1199ABB
    Argentina

    Site Not Available

  • AKH - Medical University of Vienna

    Wien, 1090
    Austria

    Site Not Available

  • ULB Hopital Erasme

    Bruxelles, 1070
    Belgium

    Site Not Available

  • Edegem - UNIV UZ Antwerpen

    Edegem, 2650
    Belgium

    Site Not Available

  • CHUM Centre de recherche

    Montreal, Quebec H2X 0A9
    Canada

    Active - Recruiting

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montreal, Quebec H2X 0A9
    Canada

    Site Not Available

  • Beijing Friendship Hospital

    Beijing, 100050
    China

    Site Not Available

  • NanFang Hosptial

    Guangzhou, 510515
    China

    Site Not Available

  • The Affiliated Hospital of Hangzhou Normal University

    Hangzhou, 310015
    China

    Site Not Available

  • Zhongshan Hospital Affiliated to Fudan University

    Shanghai, 200032
    China

    Site Not Available

  • Zhongshan Hospital Fudan University

    Shanghai, 200032
    China

    Site Not Available

  • Wuhan Union Hospital

    Wuhan, 430022
    China

    Site Not Available

  • Hvidovre Hospital

    Hvidovre, 2650
    Denmark

    Site Not Available

  • HOP Beaujon

    Clichy, 92118
    France

    Site Not Available

  • HOP Rangueil

    Toulouse, 31059
    France

    Site Not Available

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover

    Hannover, 30625
    Germany

    Site Not Available

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131
    Germany

    Site Not Available

  • Universitätsklinikum Münster

    Münster, 48149
    Germany

    Site Not Available

  • Rambam Medical Center

    Haifa, 31096
    Israel

    Site Not Available

  • Western Galilee Hospital

    Nahariya, 2210001
    Israel

    Site Not Available

  • Ospedale Civile di Baggiovara

    Baggiovara (MO), 41126
    Italy

    Site Not Available

  • ASST Grande Ospedale Metropolitano Niguarda

    Milano, 20162
    Italy

    Site Not Available

  • Azienda Ospedaliera Policlinico di Modena

    Modena, 41124
    Italy

    Site Not Available

  • A.O. Univ. Policlinico "Paolo Giaccone"

    Palermo, 90127
    Italy

    Site Not Available

  • Kitasato University Hospital

    Kanagawa, Sagamihara, 252-0375
    Japan

    Site Not Available

  • National Hospital Organization Yokohama Medical Center

    Kanagawa, Yokohama, 245-8575
    Japan

    Site Not Available

  • Osaka Metropolitan University Hospital

    Osaka, Osaka, 545-8586
    Japan

    Site Not Available

  • Amsterdam UMC, Locatie AMC

    Amsterdam, 1105 AZ
    Netherlands

    Site Not Available

  • Amsterdam UMC, location VUMC

    Amsterdam, 1105 AZ
    Netherlands

    Site Not Available

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

    Cluj-Napoca, 400000
    Romania

    Site Not Available

  • Singapore General Hospital

    Singapore, 169608
    Singapore

    Site Not Available

  • Hospital Vall d'Hebron

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Vall d'Hebron-Barcelona-47683

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Ramón y Cajal

    Madrid, 28034
    Spain

    Site Not Available

  • Hospital Puerta de Hierro

    Majadahonda, 28222
    Spain

    Site Not Available

  • University Hospital Basel

    Basel, 4031
    Switzerland

    Site Not Available

  • Aintree University Hospital

    Liverpool, L9 7AL
    United Kingdom

    Site Not Available

  • California Liver Research Institute

    Pasadena, California 91105
    United States

    Site Not Available

  • Inland Empire Clinical Trials, LLC

    Rialto, California 92377
    United States

    Site Not Available

  • Floridian Clinical Research

    Miami Lakes, Florida 33016
    United States

    Site Not Available

  • Floridian Clinical Research-Miami Lakes-68368

    Miami Lakes, Florida 33016
    United States

    Site Not Available

  • American Research Corporation

    San Antonio, Texas 78215
    United States

    Site Not Available

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