Trial results for a Phase 2 study (NCT05282121) investigating avenciguat alone or in combination with empagliflozin for liver cirrhosis with portal hypertension were posted on ClinicalTrials.gov on 2025-04-29. The study was terminated, and results showed that the combination of avenciguat and empagliflozin in patients with NASH and type 2 diabetes led to a 3.27% increase in hepatic venous pressure gradient (HVPG) from baseline.
Background
The study investigated treatments for liver cirrhosis caused by viral hepatitis (hepatitis B or C) or non-alcoholic steatohepatitis (NASH) in patients who also had high blood pressure in the portal vein (portal hypertension).
Trial design
The study (NCT05282121) was a Phase 2 trial with an enrollment of 90 participants. It was designed to evaluate avenciguat alone or in combination with empagliflozin in adults with liver cirrhosis caused by hepatitis B, hepatitis C, or non-alcoholic steatohepatitis (NASH) who had high blood pressure in the portal vein (portal hypertension). Participants took avenciguat tablets twice daily for 8 weeks. Half of the participants with NASH and type 2 diabetes also received empagliflozin tablets.
Key results
The trial, which was terminated, reported several outcome measurements after 8 weeks of treatment:
- Percentage Change in HVPG From Baseline:
- For patients with HBV receiving avenciguat, the least squares mean change was -16.06% (Standard Error: 6.66).
- For patients with HCV receiving avenciguat, the least squares mean change was -5.81% (Standard Error: 7.09).
- For patients with NASH (with or without T2DM) receiving avenciguat, the least squares mean change was 3.83% (Standard Error: 4.25).
- For patients with NASH and T2DM receiving avenciguat + empagliflozin, the least squares mean change was 3.27% (Standard Error: 5.08).
- Occurrence of a Response (> 10% Reduction From Baseline HVPG):
- 9 participants in the HBV - avenciguat group.
- 2 participants in the HCV - avenciguat group.
- 9 participants in the NASH (with or without T2DM) - avenciguat group.
- 4 participants in the NASH with T2DM - avenciguat + empagliflozin group.
- Occurrence of One or More Decompensation Events:
- 1 participant in the HBV - avenciguat group.
- 0 participants in the HCV - avenciguat group.
- 4 participants in the NASH (with or without T2DM) - avenciguat group.
- 1 participant in the NASH with T2DM - avenciguat + empagliflozin group.
What this means
The termination of this Phase 2 trial indicates that the study did not proceed as planned. While avenciguat alone showed a reduction in HVPG in patients with HBV and HCV, it led to an increase in HVPG in NASH patients. The combination of avenciguat and empagliflozin in patients with NASH and type 2 diabetes also resulted in an increase in HVPG, suggesting that this combination did not achieve the desired effect of reducing portal pressure in this specific patient population. The varied responses across different etiologies of liver cirrhosis highlight the complexity of treating portal hypertension and the need for further research into targeted therapies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05282121, titled "A Study to Test Whether BI 685509 Alone or in Combination With Empagliflozin Helps People With Liver Cirrhosis Caused by Viral Hepatitis or Non-alcoholic Steatohepatitis (NASH) Who Have High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver)," were posted on 2025-04-29 on clinicaltrials.gov.