Clinical significant portal hypertension (CSPH) high blood pressure in portal vein
Conditions
Interventions
8 weeks of treatment consisting of a 2 weeks dose up-titration period and a 6
weeks maintenance period.
20 patients in the HBV arm: treatment group 1 with 3mg BID BI 685509
20 patients in the HCV a
Sponsors
Boehringer Ingelheim
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial 2. Male or female who is >= 18 (or who is of legal age in countries where that is greater than 18) and = 10 mmHg (measured at Visit 1c), based on a local interpretation of the pressure tracing 5. Diagnosis of compensated cirrhosis due to HCV, HBV, or NASH with or without T2DM. Diagnosis of cirrhosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count
Exclusion criteria
Exclusion criteria: 1. Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], VH and / or overt / apparent HE) 2. 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) 3. 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 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 DNA detectable • Weight change >= 5% within 6 months prior screening 4. 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 5. SBP 15 at screening (Visit 1a), calculated by the central laboratory 7. Hepatic impairment defined as a Child-Turcotte-Pugh score >= B8 at screening (Visit 1a), calculated by the site, using central laboratory results 8. ALT or AST > 5 times upper limit of normal (ULN) at screening (Visit 1a), measured by the central laboratory 9. eGFR (CKD-EPI formula) 50 ng/mL (> 50 µg/L) at screening (Visit 1a), measured by the central laboratory 11. An active infection with SARS-CoV-2 (or who is known to have a positive test from screening [Visit 1a] until randomisation [Visit 2]) 12. Prior orthotopic liver transplantation 13. Prior or planned TIPS or other porto-systemic bypass procedure 14. Known portal vein thrombosis 15. History of clinically relevant orthostatic hypotension, fainting spells or blackouts due to hypotension or of unknown origin (based on Investigator judgement) 16. 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 or planned initiation of such therapies during the trial 17. Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. LADA) 18. Patients at increased risk of ketoacidosis in the opinion of the investigator. 19. Contraindication to any of the trial assessments (e.g. poor patient co-operation for gastroscopy, cardiac pacemakers for FibroScan® [if contraindicated based on local market approval] etc.) 20. Major surgery (major according to the investigator*s assessment) performed within 12 weeks prior to randomisation (Visit 2) or planned during the trial, e.g. hip replacement. 21. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening (Visit 1a), except appropriately treated basal cell carcinoma of the skin or in situ carcinom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| - occurrence of a response, which is defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment - occurrence of one or more decompensation events (i.e. ascites, VH, and / or overt 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 - occurrence of discontinuation due to hypotension or syncope during the 8-week treatment period | — |
Countries
Netherlands
Outcome results
None listed