portal hypertension MedDRA version: 20.0 Level: HLT Classification code 10036201 Term: Portal hypertensions System Organ Class: 100000004866
Conditions
Sponsors
SCS Boehringer Ingelheim Comm. V
Eligibility
Sex/Gender
All
Inclusion 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 - 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 3 months prior to screening. - documented endoscopic proof of oesophageal varices and / or gastric varices at screening or within 3 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 =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - 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 sclerosis, 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 with a sustained virological response (SVR) at screening and throughout the trial - ARLD without adequate treatment (e.g. lifestyle modification) or with ongoing pathological drinking behaviour - 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 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) 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 - Further criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment 2) response rate defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment 3) response rate defined as > 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment 4) occurrence of one or more decompensation events (i.e. ascites, VH, and / or overt HE) during the 24 week treatment period 5) occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment period 6) occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment period 7) occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment period 8) occurrence of discontinuation due to hypotension or syncope during the 24 week treatment period ;Timepoint(s) of evaluation of this end point: 1) week 8 2) week 8 3) week 24 4) week 24 5) week 8 6) week 24 7) week 8 8) week 24 | — |
Countries
Argentina, Austria, Belgium, Canada, China, Croatia, Denmark, France, Germany, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Romania, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactCT Disclosure & Data Transparency
Boehringer Ingelheim Pharma GmbH&Co KG
Outcome results
None listed