Last reviewed · How we verify

NCT05282121

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)

Terminated Phase 2 Results posted Last updated 4 September 2025
What this trial tests

Phase 2 trial testing Avenciguat in Liver Diseases in 90 participants. Terminated before completion.

Timeline
28 June 2022
Primary endpoint
23 April 2024
7 June 2024

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment90
Start date28 June 2022
Primary completion23 April 2024
Estimated completion7 June 2024
Sites31 locations across Denmark, France, Italy, Japan, Netherlands, Belgium, Austria, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 75, any sex, with Liver Diseases or Hypertension, Portal. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Change in HVPG From Baseline (Measured in mmHg) After 8 Weeks of Treatment Primary · Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in millimetre of mercury \[mmHg\]) after 8 weeks of treatment is reported. Adjusted mean (Least Square Mean) was calculated using an analysis of covariance (ANCOVA) model without imputing the missing data. The model included treatment as fixed classification effects, and baseline HVPG as a linear covariate. The random error was assumed to be normally distributed with mean 0 and variance σ².

GroupValue95% CI
Patients With HBV - Avenciguat-16.06± 6.66
Patients With HCV - Avenciguat-5.81± 7.09
Patients With NASH With or Without T2DM - Avenciguat3.83± 4.25
Patients With NASH With T2DM - Avenciguat + Empagliflozin3.27± 5.08
Occurrence of a Response, Which is Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment Secondary · Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Occurrence of a response, which is defined as \> 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment is reported.

GroupValue95% CI
Patients With HBV - Avenciguat9
Patients With HCV - Avenciguat2
Patients With NASH With or Without T2DM - Avenciguat9
Patients With NASH With T2DM - Avenciguat + Empagliflozin4
Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 8-week Treatment Period Secondary · From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage \[VH\], and / or overt Hepatic Encephalopathy \[HE\]) during the 8-week treatment period is reported.

GroupValue95% CI
Patients With HBV - Avenciguat1
Patients With HCV - Avenciguat0
Patients With NASH With or Without T2DM - Avenciguat4
Patients With NASH With T2DM - Avenciguat + Empagliflozin1
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 8-week Treatment Period Secondary · From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8-week treatment period is reported. The CTCAE grades are: 1 (mild Adverse Event \[AE\]), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

GroupValue95% CI
Patients With HBV - Avenciguat0
Patients With HCV - Avenciguat0
Patients With NASH With or Without T2DM - Avenciguat0
Patients With NASH With T2DM - Avenciguat + Empagliflozin1
Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period Secondary · From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Occurrence of discontinuation of treatment with avenciguat due to hypotension or syncope during the 8-week treatment period is reported.

GroupValue95% CI
Patients With HBV - Avenciguat0
Patients With HCV - Avenciguat0
Patients With NASH With or Without T2DM - Avenciguat0
Patients With NASH With T2DM - Avenciguat + Empagliflozin1

Adverse events — posted to ClinicalTrials.gov

Time frame: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Patients With HBV - Avenciguat
Serious: 1/14 (7%)
Deaths: 0/14
Patients With HCV - Avenciguat
Serious: 2/13 (15%)
Deaths: 0/13
Patients With NASH With or Without T2DM - Avenciguat
Serious: 6/38 (16%)
Deaths: 0/38
Patients With NASH With T2DM - Avenciguat + Empagliflozin
Serious: 0/25 (0%)
Deaths: 0/25

Serious adverse events (8 terms)

ReactionSystemPatients With HBV - Avenci…Patients With HCV - Avenci…Patients With NASH With or…Patients With NASH With T2…
PancytopeniaBlood and lymphatic system disorders
MelaenaGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
ErysipelasInfections and infestations
Herpes zosterInfections and infestations
Hepatic cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Respiratory distressRespiratory, thoracic and mediastinal disorders
Other adverse events (33 terms — click to expand)

ReactionSystemPatients With HBV - Avenci…Patients With HCV - Avenci…Patients With NASH With or…Patients With NASH With T2…
HypotensionVascular disorders
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
AscitesGastrointestinal disorders
HeadacheNervous system disorders
DyspepsiaGastrointestinal disorders
NasopharyngitisInfections and infestations
Electrocardiogram QT prolongedInvestigations
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
Pericardial effusionCardiac disorders
Dry eyeEye disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
GastritisGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Temperature regulation disorderGeneral disorders
Hepatic function abnormalHepatobiliary disorders
Hepatic steatosisHepatobiliary disorders
HypersensitivityImmune system disorders
Oral candidiasisInfections and infestations
Limb injuryInjury, poisoning and procedural complications
Electrocardiogram PR shortenedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
ParaesthesiaNervous system disorders
AsthmaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pancytopenia, Melaena, Upper gastrointestinal haemorrhage, Erysipelas, Herpes zoster, Hepatic cancer, Hepatocellular carcinoma, Respiratory distress.

Data from ClinicalTrials.gov NCT05282121 adverse events section.

Sponsor's own description

This study is open to adults with liver cirrhosis caused by hepatitis B, hepatitis C or nonalcoholic steatohepatitis (NASH). People can join this study if they have high blood pressure in the portal vein (main vessel going to the liver). The purpose of this study is to find out whether a medicine called Avenciguat (BI 685509) taken alone or in combination with a medicine called empagliflozin helps people with this condition. Participants take Avenciguat (BI 685509) as tablets twice a day for 8 weeks. Half of the participants with NASH who also have type 2 diabetes take empagliflozin as tablets once a day in addition to Avenciguat (BI 685509). Participants are in the study for about 3 months. During this time, they visit the study site about 10 times. At 2 of the visits, the doctors check the pressure in a liver vein to see whether the treatment works. This is done with a catheter (a long thin tube) and gives information about the pressure in the portal vein. The doctors also regularly check participants' health and take note of any unwanted effects.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study.
    Lawitz EJ, Lawitz EJ, Reiberger T, Schattenberg JM, et al · · 2023 · cited 10× · PMID 37889522 · DOI 10.1097/hc9.0000000000000276
  2. The rationale and study design of two phase II trials examining the effects of BI 685,509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis.
    Reiberger T, Berzigotti A, Trebicka J, Ertle J, et al · · 2023 · cited 10× · PMID 37095557 · DOI 10.1186/s13063-023-07291-3
  3. From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.
    Porada M, Bułdak Ł. · · 2025 · cited 5× · PMID 39997697 · DOI 10.3390/metabo15020072
  4. Safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509, a soluble guanylyl cyclase activator, in healthy volunteers: Results from two randomized controlled trials.
    Wong D, Seitz F, Bauer V, Giessmann T, et al · · 2024 · cited 4× · PMID 38789635 · DOI 10.1007/s00210-024-03165-w
  5. Current and investigational drugs in early clinical development for portal hypertension.
    Sakiani S, Heller T, Koh C. · · 2022 · cited 4× · PMID 36300180 · DOI 10.3389/fmed.2022.974182
  6. Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases.
    Yin Q, Zheng X, Song Y, Wu L, et al · · 2023 · cited 3× · PMID 38186653 · DOI 10.3389/fphar.2023.1272073

Verify or expand the search:

Other trials of Avenciguat

Trials testing the same drug.

Other recruiting trials for Liver Diseases

Currently open trials in the same condition.

Other Boehringer Ingelheim trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05282121.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing