A Study to Test Whether Avenciguat Helps People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) Who Had Bleeding in the Esophagus or Fluid Accumulation in the Belly

Liver Cirrhosis Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Investigate the Effects of One Dose (Up-titration to a Fixed Dose Regimen) of Oral BI 685509 on Portal Hypertension After 8 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Decompensated Cirrhosis After Their First Decompensation Event, Who Are Stabilized CTP 5-7

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06082843
• Other study ID #: 1366-0055
• Secondary ID: 2023-506083-13-0
• Status: Recruiting
• Phase: Phase 2
• Start date: January 3, 2024
• Est. completion date: August 12, 2024

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is open to adults with advanced liver cirrhosis caused by hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis or other causes. People can join the study if they have high blood pressure in the portal vein (main vessel going to the liver) and bleeding in the esophagus or fluid accumulation in the belly. The purpose of this study is to find out whether a medicine called avenciguat helps people with this condition. Participants are put into 2 groups by chance. One group takes avenciguat tablets and the other group takes placebo tablets. Placebo tablets look like avenciguat tablets but do not contain any medicine. Participants take a tablet twice a day for 8 weeks. Participants are in the study for 2 to 3 months. During this time, they visit the study site regularly. At 2 of the visits, the doctors check the pressure in the liver vein by inserting a catheter (a long thin tube) that gives information about pressure in the portal vein. The change in blood pressure is then compared between the 2 groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 12, 2024
• Est. primary completion date: July 29, 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 International Council for Harmonisation-Good Clinical Practice (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)
• Diagnosis of cirrhosis due to non-cholestatic liver disease (including Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Non-Alcoholic Steatohepatitis (NASH), alcohol-related liver disease, autoimmune hepatitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency)
• One previous clinically significant decompensation event with clinical resolution at

least 4 weeks prior start of screening (visit 1a):

• First variceal haemorrhage
• First episode of clinically significant ascites (requiring intervention in lifestyle [fluid and salt restriction] or medical treatment)
• Willing and able to undergo Hepatic Venous Pressure Gradient (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 month prior to screening (Visit 1b), with no planned dose change throughout the trial
• For patient with alcohol-related cirrhosis, abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening (Visit 1a), and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement) Further inclusion criteria apply

Exclusion Criteria:

• History of cholestatic chronic liver disease (e.g. primary biliary cholangitis, primary sclerosing cholangitis)
• Trial participants 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 Hepatitis C Virus (HCV), Sustained Virological Response (SVR) sustained for less than 1 years prior to screening
• 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 DNA detectable
• Weight change =5% within 6 months prior screening in patients with NASH
• 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 or Diastolic Blood Pressure (DBP) <70 mmHg at screening (Visit 1a)
• Hepatic impairment defined as a Child-Turcotte-Pugh score =8 at screening Further exclusion criteria apply

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis

Intervention

Drug:
• Placebo
Placebo matching Avenciguat (BI 685509)
• Avenciguat (BI 685509)
Avenciguat (BI 685509)

Locations

Country	Name	City	State
Austria	AKH - Medical University of Vienna	Vienna
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
China	Beijing Friendship Hospital	Beijing
China	NanFang Hosptial	Guangzhou
France	HOP Beaujon	Clichy
France	HOP Rangueil	Toulouse
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Münster	Münster
Japan	Shin-yurigaoka General Hospital	Kanagawa, Kawasaki
Japan	National Hospital Organization Yokohama Medical Center	Kanagawa, Yokohama
Japan	Yokohama City University Hospital	Kanagawa, Yokohama
Japan	Osaka Metropolitan University Hospital	Osaka, Osaka
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Wonju-si
Romania	Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"	Cluj-Napoca
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
United States	Northwell Health Center for Liver Disease	Manhasset	New York
United States	California Liver Research Institute	Pasadena	California
United States	Inland Empire Clinical Trials, LLC	Rialto	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Canada,  China,  France,  Germany,  Japan,  Korea, Republic of,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in HVPG from baseline measured after 8 weeks of treatment	Hepatic Venous Pressure Gradient (HVPG) measured in mmHg	Up to 8 weeks
Secondary	Occurrence of a response, which is defined as > 10% reduction from baseline HVPG after 8 weeks of treatment	HVPG measured in mmHg	Up to 8 weeks
Secondary	Occurrence of further decompensation events (i.e. ascites, variceal haemorrhage (VH), and / or overt hepatic encephalopathy (HE)) during the 8 week treatment period		Up to 8 weeks
Secondary	Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8 week treatment period	Common Terminology Criteria for Adverse Events (CTCAE)	Up to 8 weeks
Secondary	Occurrence of discontinuation due to hypotension or syncope during the 8 week treatment period		Up to 8 weeks

External Links

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