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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-506083-13-00 | Registry Identifier | CTIS |
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Company decision
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This study is open to adults with advanced liver cirrhosis caused by hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis or other causes. People can join the study if they have high blood pressure in the portal vein (main vessel going to the liver) and bleeding in the esophagus or fluid accumulation in the belly. The purpose of this study is to find out whether a medicine called avenciguat helps people with this condition.
Participants are put into 2 groups by chance. One group takes avenciguat tablets and the other group takes placebo tablets. Placebo tablets look like avenciguat tablets but do not contain any medicine. Participants take a tablet twice a day for 8 weeks.
Participants are in the study for 2 to 3 months. During this time, they visit the study site regularly. At 2 of the visits, the doctors check the pressure in the liver vein by inserting a catheter (a long thin tube) that gives information about pressure in the portal vein. The change in blood pressure is then compared between the 2 groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of placebo-matching avenciguat (BI 685509) orally twice daily (bid). Participants started the treatment with a 1 mg film-coated tablet of placebo-matching avenciguat administered bid. One week later (Visit 3), the dosage was increased to 2 mg film-coated tablets bid, and after another week, participants started on 3 mg film-coated tablet bid (Visit 4), which was maintained for the rest of the treatment. |
|
| Avenciguat | Experimental | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of avenciguat (BI 685509) orally twice daily (bid), up to a total dose of 6 milligrams (mg). The treatment period began (Visit 2) with a 1 mg film-coated tablet of avenciguat administered bid. If the dose was well-tolerated, it was increased to 2 mg film-coated tablets bid after one week (Visit 3), followed by an increase to the maintenance dose of 3 mg film-coated tablet one week later (Visit 4). If the maintenance dose of avenciguat was not well-tolerated, it was reduced, with the participants remaining on the highest tolerated dose for the rest of the treatment period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo-matching Avenciguat |
| |
| Avenciguat |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline (Measured in mmHg) After 8 Weeks of Treatment | Percentage change in hepatic venous pressure gradient (HVPG) from baseline to Week 8. | At baseline and at Week 8. |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of a Response, Defined as >10% Reduction From Baseline Hepatic Venous Pressure Gradient (HVPG) (Measured in mmHg) After 8 Weeks of Treatment | Occurrence of a response, defined as at least a 10% reduction in the hepatic venous pressure gradient (HVPG) (measured in mmHg) after 8 weeks of treatment. | At baseline and at Week 8. |
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Inclusion Criteria:
Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (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 (Visit 1a)
Diagnosis of cirrhosis due to non-cholestatic liver disease (including Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Non-Alcoholic Steatohepatitis (NASH), alcohol-related liver disease, autoimmune hepatitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency)
One previous clinically significant decompensation event with clinical resolution at least 4 weeks prior start of screening (visit 1a):
Willing and able to undergo Hepatic Venous Pressure Gradient (HVPG) measurements per protocol (based on Investigator judgement)
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
If receiving treatment with Non-Selective Beta-Blocker (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
For patient with alcohol-related cirrhosis, abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening (Visit 1a), and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement)
Further inclusion criteria apply
Exclusion Criteria:
Further exclusion criteria apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Liver Research Institute | Pasadena | California | 91105 | United States | ||
| Inland Empire Clinical Trials, LLC |
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| Label | URL |
|---|---|
| Related Info | View source |
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Once the criteria in section 'time frame frame' are fulfilled , researchers can use the following link https:// www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
For study documents upon signing of a 'Document Sharing Agreement'.For study data 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. Participants were not to be allocated to a treatment group if any of the entry criteria were violated.
Multi-national, randomised, double-blind, parallel group, placebo-controlled trial to investigate the safety and tolerability of avenciguat on top of standard of care on portal hypertension. The trial was prematurely discontinued due to the sponsor's decision.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of placebo-matching avenciguat (BI 685509) orally twice daily (bid). Participants started the treatment with a 1 mg film-coated tablet of placebo-matching avenciguat administered bid. One week later (Visit 3), the dosage was increased to 2 mg film-coated tablets bid, and after another week, participants started on 3 mg film-coated tablet bid (Visit 4), which was maintained for the rest of the treatment. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 29, 2023 | Apr 25, 2025 |
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| Drug |
1 millligram (mg), 2 mg, or 3 mg film-coated tablet |
|
|
| Occurrence of Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week Treatment Period |
Number of participants with at least one decompensation events. Ascites, variceal hemorrhage (VH), and hepatic encephalopathy were defined as further decompensations events. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. |
| Up to 46 days. |
| Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement During the 8-week Treatment Period | Number of participants with grade 3 or higher common terminology criteria for adverse events (CTCAE) hypotension or syncope base on the investigator judgment. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. | Up to 46 days. |
| Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period | Number of participants that discontinued avenciguat due to hypotension or syncope. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. | Up to 46 days. |
| Rialto |
| California |
| 92377 |
| United States |
| AKH - Medical University of Vienna | Vienna | 1090 | Austria |
| Centre Hospitalier de l'Universite de Montreal (CHUM) | Montreal | Quebec | H2X 0A9 | Canada |
| Beijing Friendship Hospital | Beijing | 100050 | China |
| NanFang Hosptial | Guangzhou | 510515 | China |
| HOP Beaujon | Clichy | 92118 | France |
| HOP Rangueil | Toulouse | 31059 | France |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | 55131 | Germany |
| Universitätsklinikum Münster | Münster | 48149 | Germany |
| Shin-yurigaoka General Hospital | Kanagawa, Kawasaki | 215-0026 | Japan |
| Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor" | Cluj-Napoca | 400162 | Romania |
| Soon Chun Hyang University Hospital Bucheon | Bucheon-si, Gyeonggi-do | 14584 | South Korea |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Ramón y Cajal | Madrid | 28034 | Spain |
| FG001 | Avenciguat | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of avenciguat (BI 685509) orally twice daily (bid), up to a total dose of 6 milligrams (mg). The treatment period began (Visit 2) with a 1 mg film-coated tablet of avenciguat administered bid. If the dose was well-tolerated, it was increased to 2 mg film-coated tablets bid after one week (Visit 3), followed by an increase to the maintenance dose of 3 mg film-coated tablet one week later (Visit 4). If the maintenance dose of avenciguat was not well-tolerated, it was reduced, with the participants remaining on the highest tolerated dose for the rest of the treatment period. |
| COMPLETED |
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| NOT COMPLETED |
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Randomized set (RS): all enrolled trial participants that were entered or randomized to the trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of placebo-matching avenciguat (BI 685509) orally twice daily (bid). Participants started the treatment with a 1 mg film-coated tablet of placebo-matching avenciguat administered bid. One week later (Visit 3), the dosage was increased to 2 mg film-coated tablets bid, and after another week, participants started on 3 mg film-coated tablet bid (Visit 4), which was maintained for the rest of the treatment. |
| BG001 | Avenciguat | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of avenciguat (BI 685509) orally twice daily (bid), up to a total dose of 6 milligrams (mg). The treatment period began (Visit 2) with a 1 mg film-coated tablet of avenciguat administered bid. If the dose was well-tolerated, it was increased to 2 mg film-coated tablets bid after one week (Visit 3), followed by an increase to the maintenance dose of 3 mg film-coated tablet one week later (Visit 4). If the maintenance dose of avenciguat was not well-tolerated, it was reduced, with the participants remaining on the highest tolerated dose for the rest of the treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Hepatic Venous Pressure Gradient (HVPG) | Mean | Standard Deviation | mmHg |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline (Measured in mmHg) After 8 Weeks of Treatment | Percentage change in hepatic venous pressure gradient (HVPG) from baseline to Week 8. | As the trial was discontinued prematurely and no patient completed the 8-week treatment period, no data were available to assess the endpoint. | Posted | At baseline and at Week 8. |
|
| ||||||||||||||||||||||
| Secondary | Occurrence of a Response, Defined as >10% Reduction From Baseline Hepatic Venous Pressure Gradient (HVPG) (Measured in mmHg) After 8 Weeks of Treatment | Occurrence of a response, defined as at least a 10% reduction in the hepatic venous pressure gradient (HVPG) (measured in mmHg) after 8 weeks of treatment. | As the trial was discontinued prematurely and no patient completed the 8-week treatment period, no data were available to assess the endpoint. | Posted | At baseline and at Week 8. |
| |||||||||||||||||||||||
| Secondary | Occurrence of Further Decompensation Events (Ascites, Variceal Hemorrhage (VH), and / or Overt Hepatic Encephalopathy (HE)) During the 8-week Treatment Period | Number of participants with at least one decompensation events. Ascites, variceal hemorrhage (VH), and hepatic encephalopathy were defined as further decompensations events. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. | Treated set (TS): all trial participants who were randomized to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | Up to 46 days. |
| |||||||||||||||||||||
| Secondary | Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement During the 8-week Treatment Period | Number of participants with grade 3 or higher common terminology criteria for adverse events (CTCAE) hypotension or syncope base on the investigator judgment. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. | Treated set (TS): all trial participants who were randomized to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | Up to 46 days. |
| |||||||||||||||||||||
| Secondary | Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period | Number of participants that discontinued avenciguat due to hypotension or syncope. As the trial was discontinued prematurely and no patient completed the 8-week treatment period, the data presented reflects the actual on-treatment period. | Treated set (TS): all trial participants who were randomized to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | Up to 46 days. |
|
All-cause mortality: From first drug administration until individual end of study. Up to 60 days. Adverse event reporting: From first administration until last drug administration plus 7-day residual effect period. Up to 53 days.
Treated set (TS): all trial participants who were randomized to the trial medication and were treated with at least one dose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of placebo-matching avenciguat (BI 685509) orally twice daily (bid). Participants started the treatment with a 1 mg film-coated tablet of placebo-matching avenciguat administered bid. One week later (Visit 3), the dosage was increased to 2 mg film-coated tablets bid, and after another week, participants started on 3 mg film-coated tablet bid (Visit 4), which was maintained for the rest of the treatment. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG001 | Avenciguat | Participants with stabilized decompensated cirrhosis due to non-cholestatic liver disease, following their first decompensation event, received 1 milligram (mg), 2 mg, or 3 mg film-coated tablets of avenciguat (BI 685509) orally twice daily (bid), up to a total dose of 6 milligrams (mg). The treatment period began (Visit 2) with a 1 mg film-coated tablet of avenciguat administered bid. If the dose was well-tolerated, it was increased to 2 mg film-coated tablets bid after one week (Visit 3), followed by an increase to the maintenance dose of 3 mg film-coated tablet one week later (Visit 4). If the maintenance dose of avenciguat was not well-tolerated, it was reduced, with the participants remaining on the highest tolerated dose for the rest of the treatment period. | 0 | 10 | 2 | 10 | 3 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus arrest | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Vulval abscess | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
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| Polyuria | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 1, 2024 | Apr 25, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006975 | Hypertension, Portal |
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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