Randomized, placebo-controlled, double blind, multi-centre Phase IIb study to evaluate the efficacy and safety of HepaStem in patients with acute on chronic liver failure (ACLF).
- Conditions
- Acute chronic liver failure10019654
- Registration Number
- NL-OMON55256
- Lead Sponsor
- Promethera Therapeutics SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
Patients must fulfill all of the following criteria in order to be eligible for
trial enrollment:
1. Are adults aged between 18 and 70 years old.
2. Have an initial diagnosis of ACLF at the investigational site.
3. Have ACLF grade 1 or 2 according to the EASL-CLIF Consortium definition.
4. Have a total bilirubin >= 5 mg/dL.
5. Are able to read, understand and give written informed consent.
If the patient is unable to fully understand the study and based on the
investigator*s judgment, the
ICF must be signed by a legal or authorized representative of the patient
according to local
regulation. In case of hepatic encephalopathy (HE), the ICF must be signed by
the patient after
encephalopathy improvement, if possible.
Enrollment criteria
Patients must fulfill all of the following criteria in order to be enrolled in
the trial at the end of the
Screening period:
1. Have completed all the procedures required at Screening.
2. Are still meeting all inclusion criteria and no exclusion criteria.
Infusion criteria
On the day of randomization and infusion, patients must fulfill all of the
following criteria in order
to be infused with the IMP (HepaStem or the Placebo):
1. Have ACLF grade 1 or 2 (before first infusion).
2. Have been diagnosed with ACLF at the investigational site according to the
EASL-CLIF
Consortium definition, no earlier than 8 days before randomization.
3. Have fibrinogen >= 80 mg/dL (as measured earlier on the same day before
infusion).
4. Have platelets >= 50 x 10³/mm³ (as measured earlier on the same day before
infusion).
5. Have no bleeding at a non-compressible site or no uncontrolled bleeding at a
compressible site as deemed by the investigator.
6. Is expected to remain hospitalized for at least 24 hours post infusion.
7. Have not experienced an adverse event (AE) considered related to the IMP and
associated
with an outcome defining an SAE (before the second infusion)
If the patient does not meet the infusion criteria prior to the first infusion,
the patient will be
considered as a screening failure.
If the patient does not meet the infusion criteria prior to the second
infusion, or the infusion
cannot be performed within the Day 8 Visit timeframe (±2 days), the infusion
will not be
performed but the Day 8 Visit and further visits should be performed according
to the protocol.
The missing infusion will not be replaced.
Patients presenting with any of the following criteria will not be included in
the study:
1. Have a MELD-Na score > 35.
2. Have underlying cirrhosis due to biliary disease.
3. Have underlying cirrhosis due to autoimmune hepatitis.
4. Have active bleeding at a non-compressible site or at a compressible site
that, in the
opinion of the investigator, poses an unacceptable risk for the patient*s
participation in the
study.
5. Have received treatment for bleeding complications during the current
hospitalization
and has a persistent high risk for re-bleeding that, in the opinion of the
investigator, poses an
unacceptable risk for the patient*s participation in the study.
6. Have a complete portal vein thrombosis.
7. Have coagulation disturbances defined as:
- fibrinogen < 80 mg/dL
- platelets < 50 x 10³/mm³
8. Are requiring chronic dialysis therapy.
9. Have had a cerebrovascular, myocardial, limb arterial thrombotic event, or
history for
both thrombotic and hemorrhagic cerebrovascular events within 12 months prior
to the Screening
and not considered stabilized by the investigator.
10. Have a previous history of myocardial infarction and/or cardiac failure,
with an ejection
fraction rate (EFR) <= 40%.
11. Have an inability to maintain mean blood pressure (BP) > 60 mmHg despite
use of
vasopressors.
12. Have severe pulmonary arterial hypertension defined as mean pulmonary
arterial
pressure (MPAP) >= 45 mmHg (or right ventricular systolic pressure >= 50 mmHg) by
echocardiography.
13. Have hepatopulmonary syndrome.
14. Are receiving mechanical ventilation due to respiratory failure.
15. Have known or suspected hypersensitivity or allergy to any of the
components of theHepaStem diluent, dimethyl sulfoxide (DMSO), or bovine serum
albumin.
16. Have a history of severe allergies to drugs and/or a history of severe
anaphylactic
reactions.
17. Have undergone a major invasive procedure within 2 weeks of randomization.
These are
open surgeries (the proper healing of the scar should be verified by the
investigator).
- Liver biopsy (transjugular or percutaneous), paracentesis, and transjugular
intrahepatic portosystemic shunt (TIPS) are not considered as major invasive
procedures.
18. Had a previous organ transplantation and/or treatment with cell-based
therapy.
19. Are accepted as High Urgency status patient by the organ allocation system.
20. Have active primary or recurrent malignant disease (including
hepatocellular carcinoma)
or have been in remission from clinically significant malignancy for < 5 years.
- Patients with cervical carcinoma in situ that has been resected with no
evidence
of recurrence or metastatic disease for at least 3 years may participate in the
study.
- Patients with basal cell or squamous epithelial skin cancers that have been
completely resected with no evidence of recurrence for at least 3 years may
participate in
the study.
21. Are receiving immunosuppressive drugs, except glucocorticoids.
- Patients receiving glucocorticoids administered for treatment of severe
alcoholic
hepatitis may participate in the study.
22. Have a contraindication to or are unwilling to take glucocorticoids to
prevent infusion-like
reaction.
23. Have persistently positive blood cultures despite 48 hours of antibiotic <b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>Survival at Day 90: Whether the patients are still alive will be recorded up to<br /><br>Day 90. Time and reason of death will be recorded.</p><br>
- Secondary Outcome Measures
Name Time Method