A clinical study to evaluate a new medicinal product VS-01 in patients with an acute episode on top of a chronic liver disease (called acute-on-chronic liver failure) who experience accumulation of fluid in the abdominal cavity (called ascites) as well as intellectual, behavioral decay and physical decay

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

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

22 Mar 2023 → 16 Oct 2025

Decision date (initial)

2024-05-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Versantis AG

External identifiers

EU CT number

2024-513706-56-00

EudraCT number

2021-002617-33

ClinicalTrials.gov

NCT05900050

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

To evaluate the efficacy of VS-01 administered intraperitoneally (i.p.) daily over 4 days on top of standard of care (SOC) vs. SOC alone in patients with ACLF grades 1, 2 or 3a as measured by Chronic Liver Failure Consortium Acute on-Chronic Liver Failure (CLIF-C ACLF) score at Day 7

Secondary objectives 2

1. To evaluate the efficacy of VS-01 administered i.p. daily over 4 days on top of SOC vs. SOC alone in patients with ACLF grades 1, 2 or 3a with respect to: a. Mortality rate; b. Time to death; c. ACLF grade change and time to ACLF resolution; d. Transplant-free survival;
2. To characterize the safety and tolerability of VS-01 in ACLF patients following i.p. administration of VS-01

Conditions and MedDRA coding

Acute-on-chronic liver failure (ACLF) is characterized by hepatic and extrahepatic organ dysfunction and/or failure and highly activated systemic inflammation. It leads to an accumulation of different metabolites, interalias ammonia, which cannot be metabolized. Hyperammonemia leads to Hepatic Encephalopathy (HE). ACLF is a major cause of death in cirrhosis, with an approximately 50% mortality rate. The selected patient population is ACLF grade 1, 2 or 3a patients.

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Patients with ACLF Grade 1, 2 or 3a according to EASL-CLIF criteria (organ failures will be calculated based on the CLIF-C OF score) in the presence of liver cirrhosis of any underlying etiology
2. 2. Onset of ACLF not more than 14 days before BL;
3. 3. Presence of ascites requiring diagnostic or therapeutic paracentesis;
4. 4. Patients with a dry body weight ≥ 40 kg and < 140 kg;
5. 5. Men and women ≥ 18 and ≤ 79 years of age on the day of signing Patient Informed Consent Document (PICD);
6. 6. Informed consent: a. Ability to understand the PICD and comply with the protocol and sign the PICD or a legal representative can sign the PICD on behalf of the patient in accordance with local law and institutional policy; b. Signed and dated PICD obtained prior to performing any study-related procedure including SCR.

Exclusion criteria 18

1. 1. Presence of any of the following organ failure(s) as per the EASL-CLIF criteria and/or adapted from CLIF-COF/CLIF-SOFA scores: a. Respiratory failure mechanical ventilation; b. Coagulation failure with an INR > 3.2 or platelet count ≤ 20 x 10^9/L; c. Severe cardiovascular failure requiring the use of high doses of 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 in case of hepatorenal syndrome [HRS] is not an exclusion criterion; d. HE West Haven grade 4;
2. 2. ACLF grade 3b: Presence of four or more organ failures according to EASL-CLIF criteria (organ failures will be calculated based on CLIF-C OF score);
3. 3. Presence of spontaneous or secondary bacterial peritonitis (i.e., neutrophil counts > 250/mm3 in ascitic fluid);
4. 4. Presence of uncontrolled severe infection with hemodynamic instability or shock; patients may be enrolled provided anti-infectives have been administered for at least 48 h before BL with an appropriate response prior to randomization
5. 5. Patients with poorly controlled seizure disorder;
6. 6. Patients with medical history of gastro-intestinal bleeding over the past 7 days prior to BL, acute bleeding or bleeding upon paracentesis at SCR or BL;
7. 7. Contraindication for paracentesis according to the EASL Clinical Practice Guidelines 2018 and AASLD guideline on the treatment of ascites, spontaneous bacterial peritonitis and HRS-AKI for the management of patients with decompensated cirrhosis;
8. 8. Coagulation disorders such as disseminated intravascular coagulation (DIC) or hemophilia;
9. 9. Potential or known hypersensitivity to liposomes;
10. 10. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;
11. 11. Patients after organ transplantation receiving immunosuppressive medication;
12. 12. Any severe disease considered to be potentially detrimental at the discretion of the PI. This includes but is not limited to hepatocellular carcinoma (HCC) outside Milan criteria, cholangiocarcinoma, extrahepatic cancer over the past 2 years, or people who inject drugs ;
13. 13. Need for RRT or any extracorporeal liver support device (e.g., MARS® , Prometheus® , Plasmapheresis);
14. 14. Alfapump® in place to manage ascites;
15. 15. Pregnancy and lactation;
16. 16. Women of child-bearing potential who are not willing to use adequate contraception;
17. 17. Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.
18. AND FRANCE ONLY: 18. Patients who lack social security affiliation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CLIF-C ACLF score at Day 7

Secondary endpoints 2

1. Outcome a) 90 day – mortality; b) 28 day – mortality; c) Time to death through Day 90; d) Time to death through Day 28; e) Change in ACLF grade through/at Days 7 and 28: - Rate of ACLF resolution; - Time to ACLF resolution; - Rate of ≥ one ACLF grade regression; - Time to ≥ one ACLF grade regression; f) Transplant-free survival through/at Day 90; g) Transplant-free survival through/at Day 28
2. Safety a) Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.

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 6

Locations

6 EU/EEA countries · 16 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 106 files

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

Application history

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