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A Study to Test Whether BI 685509 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

Primary Purpose

Hypertension, Portal, Liver Cirrhosis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Placebo
BI 685509
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension, Portal

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 sclerosis, 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Placebo

    BI 685509

    Arm Description

    This trial contemplates a dose-titration period, depending on dose tolerability.

    Outcomes

    Primary Outcome Measures

    Percentage change in HVPG from baseline measured after 8 weeks of treatment
    Hepatic Venous Pressure Gradient (HVPG) measured in mmHg

    Secondary Outcome Measures

    Occurrence of a response, which is defined as > 10% reduction from baseline HVPG after 8 weeks of treatment
    HVPG measured in mmHg
    Occurrence of further decompensation events (i.e. ascites, variceal haemorrhage (VH), and / or overt hepatic encephalopathy (HE)) during the 8 week treatment period
    Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8 week treatment period
    Common Terminology Criteria for Adverse Events (CTCAE)
    Occurrence of discontinuation due to hypotension or syncope during the 8 week treatment period

    Full Information

    First Posted
    October 9, 2023
    Last Updated
    October 9, 2023
    Sponsor
    Boehringer Ingelheim
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06082843
    Brief Title
    A Study to Test Whether BI 685509 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

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 6, 2023 (Anticipated)
    Primary Completion Date
    May 28, 2024 (Anticipated)
    Study Completion Date
    June 11, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Boehringer Ingelheim

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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 BI 685509 helps people with this condition. Participants are put into 2 groups by chance. One group takes BI 685509 tablets and the other group takes placebo tablets. Placebo tablets look like BI 685509 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypertension, Portal, Liver Cirrhosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    40 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Experimental
    Arm Title
    BI 685509
    Arm Type
    Experimental
    Arm Description
    This trial contemplates a dose-titration period, depending on dose tolerability.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo matching BI 685509
    Intervention Type
    Drug
    Intervention Name(s)
    BI 685509
    Intervention Description
    BI 685509
    Primary Outcome Measure Information:
    Title
    Percentage change in HVPG from baseline measured after 8 weeks of treatment
    Description
    Hepatic Venous Pressure Gradient (HVPG) measured in mmHg
    Time Frame
    Up to 8 weeks
    Secondary Outcome Measure Information:
    Title
    Occurrence of a response, which is defined as > 10% reduction from baseline HVPG after 8 weeks of treatment
    Description
    HVPG measured in mmHg
    Time Frame
    Up to 8 weeks
    Title
    Occurrence of further decompensation events (i.e. ascites, variceal haemorrhage (VH), and / or overt hepatic encephalopathy (HE)) during the 8 week treatment period
    Time Frame
    Up to 8 weeks
    Title
    Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8 week treatment period
    Description
    Common Terminology Criteria for Adverse Events (CTCAE)
    Time Frame
    Up to 8 weeks
    Title
    Occurrence of discontinuation due to hypotension or syncope during the 8 week treatment period
    Time Frame
    Up to 8 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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 sclerosis, 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Boehringer Ingelheim
    Phone
    1-800-243-0127
    Email
    clintriage.rdg@boehringer-ingelheim.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Once the criteria in section 'time frame frame' are fulfilled , researchers can use the following link https:// www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
    IPD Sharing Time Frame
    After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
    IPD Sharing Access Criteria
    For study documents upon signing of a 'Document Sharing Agreement'.For study data 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
    IPD Sharing URL
    https://www.mystudywindow.com/msw/datasharing
    Links:
    URL
    http://www.mystudywindow.com
    Description
    Related Info

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    A Study to Test Whether BI 685509 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

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