A study to test whether two different doses of BI 685509 help people with liver cirrhosis and high blood pressure in the portal vein (main vessel going to the liver)
- Conditions
- portal hypertensionMedDRA version: 20.0Level: HLTClassification code 10036201Term: Portal hypertensionsSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2021-001285-38-DE
- Lead Sponsor
- Boehringer Ingelheim Pharma GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 78
- 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
- Clinical signs of 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
- CSPH defined as baseline HVPG = 10 mmHg, based on a local interpretation of the pressure tracing
- 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 109/L [150 x 103/µL], nodular liver surface on imaging or splenomegaly)
- 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)
- 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, with no planned dose change throughout the trial
- If receiving treatment with NSBBs or carvedilol must be on a stable dose for at least 1 months prior to screening, with no planned dose change throughout the trial
- WOCBP must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly from the randomisation visit until 7 days after the last treatment in this trial. The patient must agree to periodic pregnancy testing during participation in the trial.
- Men able to father a child and who have a female sexual partner of CBP, must use a condom with or without spermicide, or adopt complete sexual abstinence, or be vasectomised (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate), from the randomisation visit until 7 days after the last treatment in this trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
- Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], VH and / or apparent HE)
- History of other forms of chronic liver disease (e.g. non-alcoholic steatohepatitis [NASH], Hepatitis B virus [HBV], untreated HCV, autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, Wilson’s disease, haemachromatosis, alpha-1 antitrypsin [A1At] deficiency)
- 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 (Visit 1a), or, must take curative anti-viral
therapy with direct-acting anti-virals throughout the trial
- ARLD without adequate treatment (e.g. lifestyle modification) or with ongoing pathological drinking behaviour (misuse / abuse based on Investigator judement)
- 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
- SBP < 100 mmHg and DBP < 70 mmHg at screening
- Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by the central laboratory
- Hepatic impairment defined as a Child-Turcotte-Pugh score = B8 at screening, calculated by the site, using central laboratory results
- ALT or AST > 5 times upper limit of normal (ULN) at screening, measured by the central laboratory
- eGFR (CKD-EPI formula) < 20 mL/min/1.73 m2 at screening, measured by the central laboratory
- Alpha-fetoprotein > 50 ng/mL (> 50 µg/L) at screening, measured by the central laboratory
- An active infection with SARS-CoV-2 (or who is known to have a positive test from screening until randomisation)
- Prior orthotopic liver transplantation
- Prior or planned TIPS or other porto-systemic bypass procedure
- Known portal vein thrombosis
- History of clinically relevant orthostatic hypotension, fainting spells or blackouts due to hypotension or of unknown origin (based on Investigator judgement)
- Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial
- QTcF-interval > 450 ms in men or > 470 ms in women at screening (Visit 1a), a family
history of long QT syndrome, or concomitant use of therapies with a known risk of
Torsade de Pointes at screening (Visit 1a) or planned initiation of such therapies during
the trial
- Further criteria apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The trial will compare two doses of BI 685509 (2 mg and 3 mg BID) with placebo, on top of standard of care, in patients with CSPH in compensated alcohol-related cirrhosis. The primary objective is to estimate the mean difference between treatment groups with placebo in percentage change in HVPG from baseline measured after 24 weeks. The primary treatment comparison will be made for treated patients with baseline HVPG measurements (Full Analysis Set, FAS) as if all patients took randomised treatment for the duration of the trial. ;Secondary Objective: Safety and tolerability will also be investigated.;Primary end point(s): percentage change in HVPG from baseline (measured in mmHg) after 24 weeks of treatment;Timepoint(s) of evaluation of this end point: week 24
- Secondary Outcome Measures
Name Time Method