A Study to Test Whether Two Different Doses of Avenciguat Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Live

Hypertension, Portal Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Investigate the Effects of Two Doses (Up-titration to a Fixed Dose Regimen) of Oral BI 685509 on Portal Hypertension After 24 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Compensated Cirrhosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05161481
• Other study ID #: 1366-0021
• Secondary ID: 2021-001285-38
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 3, 2022
• Est. completion date: October 9, 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 and 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 helps people with this condition. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of Avenciguat as tablets twice a day. Participants in the placebo group take placebo as tablets twice a day. Placebo tablets look like Avenciguat tablets but do not contain any medicine. Participants are in the study for about 8 months. During this time, they visit the study site about 14 times. At 3 of the visits, the doctors check the pressure in a liver vein. This is done with a catheter (a long thin tube) and gives information about the pressure in the portal vein. The change in blood pressure is then compared between the 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: Active, not recruiting
• Enrollment: 80
• Est. completion date: October 9, 2024
• Est. primary completion date: September 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

2. 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

3. 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 or within 6 months prior to screening.

• documented endoscopic proof of oesophageal varices and / or gastric varices at screening or within 6 months prior to screening
• documented endoscopic-treated oesophageal varices as preventative treatment

4. CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) = 10 mmHg, based on a local interpretation of the pressure tracing

5. Diagnosis of compensated alcohol-related cirrhosis. Diagnosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count < 150 x 10^9/L [150 x 10^3/µL], nodular liver surface on imaging or splenomegaly)

6. Abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening, and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement)

7. Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement)

8. If receiving statins must be on a stable dose for at least 3 months prior to screening, with no planned dose change throughout the trial Further inclusion criteria apply.

Exclusion Criteria:

1. Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic Encephalopathy (HE))

2. History of other forms of chronic liver disease (e.g. non-alcoholic steatohepatitis (NASH), Hepatitis B virus (HBV), untreated Hepatitis C Virus (HCV), autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency)

3. Has received curative anti-viral therapy with direct-acting anti-virals within the last 2 years for HCV, or, if such treatment was > 2 years ago and there is no sustained virological response (SVR) at screening, or, must take curative anti-viral therapy with direct-acting anti-virals throughout the trial

4. Alcohol-Related Liver Disease (ARLD) without adequate treatment (e.g. lifestyle modification) or with ongoing pathological drinking behaviour (misuse / abuse based on Investigator judgement)

5. 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

6. Systolic Blood Pressure (SBP) < 100 mmHg and Diastolic Blood Pressure (DBP) < 70 mmHg at screening

7. Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by the central laboratory

8. Hepatic impairment defined as a Child-Turcotte-Pugh score = B8 at screening, calculated by the site, using central laboratory results Further exclusion criteria apply.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal

Intervention

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

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Caba
Austria	Medical University of Innsbruck	Innsbruck
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	Beijing Youan Hospital, Capital Medical University	Beijing
China	NanFang Hosptial	Guangzhou
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
Croatia	University Hospital Dubrava	Zagreb
Denmark	Hvidovre Hospital	Hvidovre
France	HOP d'Angers	Angers
France	HOP Rangueil	Toulouse
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Münster	Münster
Germany	St. Josefs-Hospital, Wiesbaden	Wiesbaden
Israel	Western Galilee Hospital	Nahariya
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Azienda Ospedaliera Policlinico di Modena	Modena
Italy	A.O. Univ. Policlinico "Paolo Giaccone"	Palermo
Italy	Poli Univ A. Gemelli	Roma
Japan	Shin-yurigaoka General Hospital	Kanagawa, Kawasaki
Japan	Kitasato University Hospital	Kanagawa, Sagamihara
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, Gangwon State
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Portugal	ULS de Santa Maria, E.P.E	Lisboa
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
Spain	Hospital Puerta de Hierro	Majadahonda
Switzerland	Ospedale Regionale di Lugano	Viganello
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	St Mary's Hospital	London
United States	Northwell Health Center for Liver Disease	Manhasset	New York
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 at the Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Canada,  China,  Croatia,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Romania,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatment		at baseline, at week 24
Secondary	Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment		at baseline, at week 8
Secondary	Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment		at baseline, at week 8
Secondary	Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment		at baseline, at week 24
Secondary	Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage (VH), and/or overt Hepatic Encephalopathy (HE)) during the 24 week treatment period		up to 24 weeks
Secondary	Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment period		up to 8 weeks
Secondary	Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment period		up to 24 weeks
Secondary	Occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment period		up to 8 weeks
Secondary	Occurrence of discontinuation due to hypotension or syncope during the 24 week treatment period		up to 24 weeks

External Links

•   Related Info