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)

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05282121
Collaborator
(none)
80
2
4
14.1
40
2.8

Study Details

Study Description

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 BI 685509 taken alone or in combination with a medicine called empagliflozin helps people with this condition.

Participants take 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 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 26, 2022
Anticipated Primary Completion Date :
Jun 30, 2023
Anticipated Study Completion Date :
Jul 28, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: BI 685509 HBV treatment group

Hepatitis B Virus (HBV)

Drug: BI 685509
BI 685509

Experimental: BI 685509 HCV treatment group

Hepatitis C Virus (HCV)

Drug: BI 685509
BI 685509

Experimental: BI 685509 NASH treatment group

Non-Alcoholic Steatohepatitis (NASH)

Drug: BI 685509
BI 685509

Experimental: BI 685509 + empagliflozin NASH treatment group

Drug: BI 685509
BI 685509

Drug: Empagliflozin
Empagliflozin

Outcome Measures

Primary Outcome Measures

  1. Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline [At baseline and at week 8]

Secondary Outcome Measures

  1. Occurrence of a response [At baseline and at week 8]

    defined as > 10 percent (%) reduction from baseline HVPG

  2. Occurrence of one or more decompensation events [Up to 8 weeks]

    i. e. ascites, Variceal Haemorrhage (VH), and / or overt Hepatic Encephalopathy (HE)

  3. Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement [Up to 8 weeks]

  4. Occurrence of discontinuation due to hypotension or syncope [Up to 8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 3 months prior to screening (Visit 1b).

  • documented endoscopic proof of oesophageal varices and / or gastric varices at screening (Visit 1b) or within 3 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 3 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 AKH - Medical University of Vienna Wien Austria 1090
2 CHUM Centre de recherche Montreal Quebec Canada H2X 0A9

Sponsors and Collaborators

  • Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT05282121
Other Study ID Numbers:
  • 1366-0029
  • 2021-005171-40
First Posted:
Mar 16, 2022
Last Update Posted:
Aug 11, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 11, 2022