Clinical trial NCT05282121: 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)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Liver Diseases
Hypertension, Portal
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 90
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change in HVPG From Baseline (Measured in mmHg) After 8 Weeks of Treatment
timeFrame: Before the first intake of trial medication (baseline), and after 8 weeks of treatment.
Secondary outcomes:
measure: Occurrence of a Response, Which is Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment
timeFrame: Before the first intake of trial medication (baseline), and after 8 weeks of treatment.
measure: Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 8-week Treatment Period
timeFrame: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.
measure: Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 8-week Treatment Period
timeFrame: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.
measure: Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period
timeFrame: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 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: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
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: Guangzhou
country: China
facility: NanFang Hosptial
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Clichy
country: France
facility: HOP Beaujon
city: Toulouse
country: France
facility: HOP Rangueil
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Hospital
city: Baggiovara (MO)
country: Italy
facility: Ospedale Civile di Baggiovara
city: Modena
country: Italy
facility: Azienda Ospedaliera Policlinico di Modena
city: Palermo
country: Italy
facility: Policlinico "Paolo Giaccone"
city: Kanagawa, Yokohama
country: Japan
facility: National Hospital Organization Yokohama Medical Center
city: Osaka, Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
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
Study officials:
References: