Clinical trial NCT06082843: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertension, Portal
Liver Cirrhosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-10-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline (Measured in mmHg) After 8 Weeks of Treatment
timeFrame: At baseline and at Week 8.
Secondary outcomes:
measure: Occurrence of a Response, Defined as >10% Reduction From Baseline Hepatic Venous Pressure Gradient (HVPG) (Measured in mmHg) After 8 Weeks of Treatment
timeFrame: At baseline and at Week 8.
measure: Occurrence of Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week Treatment Period
timeFrame: Up to 46 days.
measure: Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement During the 8-week Treatment Period
timeFrame: Up to 46 days.
measure: Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period
timeFrame: Up to 46 days.
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC
state: California
city: Vienna
country: Austria
facility: AKH - Medical University of Vienna
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Beijing
country: China
facility: Beijing Friendship Hospital
city: Guangzhou
country: China
facility: NanFang Hosptial
city: Clichy
country: France
facility: HOP Beaujon
city: Toulouse
country: France
facility: HOP Rangueil
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Kanagawa, Kawasaki
country: Japan
facility: Shin-yurigaoka General Hospital
city: Bucheon-si, Gyeonggi-do
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Cluj-Napoca
country: Romania
facility: Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
Study officials:
References: