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.
- Conditions
- Clinical significant portal hypertension (CSPH)high blood pressure in portal vein10057166
- Registration Number
- NL-OMON53952
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 5
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 <= 75 years old at screening (Visit 1a)
3. Clinical signs of 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 6 months prior to screening (Visit 1b).
• documented endoscopic proof of oesophageal varices and / or gastric varices
at screening (Visit 1b) or within 6 months prior to screening (Visit 1b)
• documented endoscopic-treated oesophageal varices as preventative treatment
4. CSPH defined as baseline HVPG >= 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 < 150 x
109/L [150 x 103/µL], nodular liver surface on imaging or splenomegaly etc.)
Diagnosis of NASH based on either
• Current or historic histological diagnosis of NASH OR steatosis
OR
• Clinical diagnosis of NASH based on historic or current imaging
diagnosis of fatty liver (Fibroscan, US, MRI, CT) AND at least 2
current or historic comorbidities of the metabolic syndrome
(overweight/obesity, T2DM, hypertension, hyperlipidemia)
6. Willing and able to undergo HVPG measurements per protocol (based on
Investigator judgement)
7. 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
8. If receiving treatment with 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
9. If receiving pioglitazone, GLP1-agonists, or vitamin E must be on a stable
dose for at least 3 months prior to screening (Visit 1b), with no planned dose
change throughout the trial
10. 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 (Visit
2) until 7 days after the last treatment in this trial. The patient must agree
to periodic pregnancy testing during participation in the trial.
11. 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 (Visit
2) until 7 days after the last treatment in this trial.
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 < 100 mmHg and DBP < 70 mmHg at screening (Visit 1a)
6. Model of End-stage Liver Disease (MELD) score of > 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) < 20 mL/min/1.73 m2 at screening (Visit 1a), measured
by the
central laboratory
10. Alpha-fetoprotein > 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method