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)

Liver Diseases Clinical Trial

Official title:

Randomised, Open-label and Parallel Group Trial to Investigate the Effects of Oral BI 685509 Alone or in Combination With Empagliflozin on Portal Hypertension After 8 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Compensated Cirrhosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05282121
• Other study ID #: 1366-0029
• Secondary ID: 2021-005171-4020
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 26, 2022
• Est. completion date: June 20, 2024

Study information

• Verified date: May 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: June 20, 2024
• Est. primary completion date: May 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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
• Further inclusion criteria apply

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
• Further exclusion criteria apply

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal
• Liver Diseases

Intervention

Drug:
• Avenciguat (BI 685509)
Avenciguat (BI 685509)
• Empagliflozin
Empagliflozin

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Hospital Italiano de Buenos Aires	Caba
Austria	AKH - Medical University of Vienna	Wien
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
China	Beijing Friendship Hospital	Beijing
China	NanFang Hosptial	Guangzhou
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
China	Zhongshan Hospital Fudan University	Shanghai
Denmark	Hvidovre Hospital	Hvidovre
France	HOP Beaujon	Clichy
France	HOP Rangueil	Toulouse
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Münster	Münster
Israel	Rambam Medical Center	Haifa
Israel	Western Galilee Hospital	Nahariya
Italy	Ospedale Civile di Baggiovara	Baggiovara (MO)
Italy	Azienda Ospedaliera Policlinico di Modena	Modena
Italy	A.O. Univ. Policlinico "Paolo Giaccone"	Palermo
Japan	National Hospital Organization Yokohama Medical Center	Kanagawa, Yokohama
Japan	Osaka Metropolitan University Hospital	Osaka, Osaka
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Romania	Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"	Cluj-Napoca
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Ramón y Cajal	Madrid
United States	Floridian Clinical Research	Miami Lakes	Florida
United States	California Liver Research Institute	Pasadena	California
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	American Research Corporation	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline		At baseline and at week 8
Secondary	Occurrence of a response	defined as > 10 percent (%) reduction from baseline HVPG	At baseline and at week 8
Secondary	Occurrence of one or more decompensation events	i. e. ascites, Variceal Haemorrhage (VH), and / or overt Hepatic Encephalopathy (HE)	Up to 8 weeks
Secondary	Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement		Up to 8 weeks
Secondary	Occurrence of discontinuation due to hypotension or syncope		Up to 8 weeks

External Links

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