A Study to See if an Investigational Medicine Called VS-01 Can Help and How Safe it is in the Treatment of Patients with Overt Hepatic Encephalopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Versantis AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Metabolism [G03]

Trial duration

18 Sep 2025 → 19 Dec 2025

Decision date (initial)

2025-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Versantis AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of two different dwell times (3 hours and 4 hours) of i.p. VS-01, administered once daily for up to 4 days on top of SOC compared to SOC alone in treating OHE in patients with AD of liver cirrhosis or ACLF grade 1 measured by time to improvement of OHE.

Secondary objectives 2

1. To evaluate the safety and tolerability of two different dwell times (3 hours and 4 hours) of i.p. VS-01 administered once daily for up to 4 days on top of SOC compared to SOC alone in patients with OHE and AD of liver cirrhosis or ACLF grade 1.
2. To evaluate the PK and PD of two different dwell times (3 hours and 4 hours) of i.p. VS-01.

Conditions and MedDRA coding

Patients with overt hepatic encephalopathy (OHE) and acute decompensation (AD) of liver cirrhosis or acute-on chronic liver failure (ACLF) grade 1

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with liver cirrhosis of any underlying etiology (liver cirrhosis diagnosed by standard clinical criteria, imaging findings, and/or histology) who are diagnosed with OHE (according to HEGI) in the presence of: AD (defined as the onset or worsening of ascites, hepatic encephalopathy, gastrointestinal (GI) bleeding, or any combination of them with or without infection); or ACLF grade 1 according to EASL-CLIF criteria;
2. Presence of ascites requiring diagnostic or therapeutic paracentesis
3. Fasting blood ammonia > upper limit of normal (ULN) at baseline (BL)
4. Patients with a dry body weight ≥40 kg and <140 kg
5. Male and female patients ≥18 to <80 years of age on the day of signing the informed consent form (ICF)
6. Patients willing and able to provide written informed consent. If the patient is not capable of giving consent, or is unable to fully understand or sign the written informed consent based on the Investigator’s judgment, the ICF must be signed by a legally authorized representative (LAR) of the patient in accordance with local regulation

Exclusion criteria 16

1. ACLF grade 2 or higher as defined by EASL-CLIF criteria
2. Presence of spontaneous or secondary bacterial peritonitis (i.e., neutrophil counts >250/mm 3 in ascitic fluid)
3. Contraindication for paracentesis according to the EASL Clinical Practice Guidelines 2018, and the American Association for the Study of Liver Diseases (AASLD) Guideline on the Treatment of Ascites, Spontaneous Bacterial Peritonitis, and Hepatorenal Syndrome 2021
4. Alfapump® in place to manage ascites
5. Known hypersensitivity to liposomes, history of mastocytosis, multiple hypersensitivities, or similar diseases known to be associated with an increased risk of allergic/anaphylactoid reactions
6. Upper GI bleeding within the last 7 days prior to BL, acute bleeding or bleeding upon paracentesis at SCR or BL
7. Poorly controlled seizure disorder
8. Respiratory failure requiring invasive mechanical ventilation
9. Severe circulatory failure requiring the use of high dose vasopressors (e.g., dopamine >15 µg/kg/min, or epinephrine >0.1 µg/kg/min, or norepinephrine >0.1 µg/kg/min); the use of terlipressin or low-dose norepinephrine to treat hepatorenal syndrome is not an exclusion criterion
10. Uncontrolled severe infection with hemodynamic instability or shock; patients may be enrolled provided anti-infectives have been administered for at least 48 hours prior to BL with an appropriate response as assessed by the PI
11. Need for renal replacement therapy (RRT) or any extracorporeal liver support device
12. Any significant disease considered to be potentially detrimental or would preclude the patient from participating in and completing the study as assessed by the PI. This includes but is not limited to hepatocellular carcinoma outside Milan criteria, cholangiocarcinoma, extrahepatic cancer over the past 2 years, or people who inject drugs
13. Individuals for whom the PI deems that study participation would be unsafe or not in the interest of the patient
14. Pregnancy or lactation
15. Women of childbearing potential and non-sterile male patients who are not willing to use adequate contraception from SCR to 30 days after the final dose of investigational medicinal product (IMP)
16. Participation in another interventional clinical trial within 30 days of SCR

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to improvement of OHE as assessed by HEGI. Improvement is defined as: a) A reduction of HE grades 4 or 3 to grade ≤2, or b) A reduction of HE grade 2 to grade <2.

Secondary endpoints 2

1. Safety and tolerability defined as: a) The incidence and severity (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0 grade) of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), comprising the evaluation of vital signs, ECG parameters, and laboratory parameters.
2. PK/PD: a) PK (for active treatment arms): blood and peritoneal fluid concentration-time profile of BL-corrected citric acid and lipids in patients treated with VS-01. b) PD (for all arms): change from BL in fasting blood and peritoneal fluid ammonia levels.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Versantis AG

Sponsor organisation

Versantis AG

Address

Technoparkstrasse 1

City

Zurich

Postcode

8005

Country

Switzerland

Scientific contact point

Organisation

Versantis AG

Contact name

Head of Clinical Operations

Public contact point

Organisation

Versantis AG

Contact name

Head of Clinical Operations

Third parties 5

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications