Clinical trial NCT05161481: 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 Liver)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertension, Portal
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-12-17
Enrollment: 80
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline After 24 Weeks of Treatment
timeFrame: From first administration of trial medication up to 24 weeks.
Secondary outcomes:
measure: Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline, Measured in Millimeters of Mercury (mmHg), After 8 Weeks of Treatment
timeFrame: From first administration of trial medication up to 8 weeks.
measure: Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment
timeFrame: From first administration of trial medication up to 8 weeks.
measure: Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 24 Weeks of Treatment
timeFrame: From first administration of trial medication up to 24 weeks.
measure: Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 24 Week Treatment Period
timeFrame: From first administration of trial medication up to 24 weeks.
measure: Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the First 8 Weeks of the Treatment Period
timeFrame: From first administration of trial medication up to 8 weeks.
measure: Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 24 Week Treatment Period
timeFrame: From first administration of trial medication up to 24 weeks.
measure: Occurrence of Discontinuation Due to Hypotension or Syncope During the First 8 Weeks of the Treatment Period
timeFrame: From first administration of trial medication up to 8 weeks.
measure: Occurrence of Discontinuation Due to Hypotension or Syncope During the 24 Week Treatment Period
timeFrame: From first administration of trial medication up to 24 weeks.
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: Miami Lakes
country: United States
facility: Floridian Clinical Research-Miami Lakes-68368
state: Florida
city: Manhasset
country: United States
facility: Northwell Health Center for Liver Disease
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Wien
country: Austria
facility: AKH - Medical University of Vienna
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Beijing
country: China
facility: Beijing Friendship Hospital
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
city: Guangzhou
country: China
facility: NanFang Hosptial
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Zagreb
country: Croatia
facility: University Hospital Dubrava
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Angers
country: France
facility: HOP d'Angers
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: Wiesbaden
country: Germany
facility: St. Josefs-Hospital, Wiesbaden
city: Nahariya
country: Israel
facility: Western Galilee Hospital
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Modena
country: Italy
facility: Azienda Ospedaliera Policlinico di Modena
city: Palermo
country: Italy
facility: Policlinico "Paolo Giaccone"
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Kanagawa, Kawasaki
country: Japan
facility: Shin-yurigaoka General Hospital
city: Kanagawa, Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama City University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: National Hospital Organization Yokohama Medical Center
city: Osaka, Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Bucheon-si, Gyeonggi-do
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Wonju-si, Gangwon State
country: Korea, Republic of
facility: Yonsei University Wonju Severance Christian Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Lisboa
country: Portugal
facility: ULS de Santa Maria, E.P.E
city: Cluj-Napoca
country: Romania
facility: Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor"
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Viganello
country: Switzerland
facility: Ospedale Regionale di Lugano
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
References: