Hepatocyte transplantation in paediatric acute liver failure Digestive System
Conditions
Interventions
This is an open-label, single-centre study first-in-man study. The study will be conducted using the Simon two-stage design. Nine patients will be recruited during stage 1 of the study. Once 9 patient
Sponsors
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Infant or child (male or female) under 16 years of age at recruitment 2. Written informed consent obtained from a parent / legal guardian 3. Presence of ALF, defined as a multisystemic disorder in which severe impairment of liver function with or without encephalopathy occurs in association with hepatocellular necrosis reflected as synthetic liver failure in a child with no recognised underlying chronic liver disease. Children must fit one of the ALF categories 4. Willing and able to comply with the study visit schedule
Exclusion criteria
Exclusion criteria: 1. Severe ascites causing high intra-abdominal pressure and / or respiratory compromise 2. Intra-abdominal sepsis suspected or proven 3. Clinical condition too unstable to tolerate procedure without compromise 4. Proven preexisting allergy or intolerance to alginate on medical history 5. Proven pre-existing allergy to gentamicin on medical history; 6. Intraperitoneal or intra-abdominal malignancy 7. Adhesions or fistulae to anterior abdominal wall 8. Children who weigh in excess of 33kg 9. Pregnant or lactating patients 10. Female patients of childbearing potential who are not willing to use highly effective methods of contraception to prevent pregnancy or abstain from heterosexual activity for 52 weeks post treatment. 11. Male patients who are not willing to use an effective method of contraception (condom, vasectomy, sexual abstinence) for 52 weeks post treatment, when engaging in sexual activity with a female of childbearing potential 12. Participation in concurrent therapeutic trial for ALF 13. Imminent Liver transplantation expected within 12 hours of infusion 14. Total Hepatectomy 15. Dependent on Extracorporeal Membrane Oxygenation (ECMO) 16. Previous liver transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety will be measured using data collected on moderate to severe (including life-threatening and death) adverse event occurrences due to the product in the first 52 weeks post-procedure (Baseline to 52 weeks) 2. Tolerability will be measured using data collected on the proportion of initiated infusion where >80% of the infusion is received by the patient (Day of infusion) 3. Biological activity will be measured using data collected on survival with a native liver at 24 weeks post-treatment (baseline to 24 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in blood marker levels including haematological, biochemical and coagulation measured using standard medical laboratory methods at baseline to 52 weeks post-treatment. This includes changes in full blood count and differentials, INR, APTT, fibrinogen, Serum levels of ALT, AST, Creatine Kinase, Total bilirubin, Conjugated bilirubin, Alkaline phosphatase, Albumin, total protein, serum urea, serum levels of sodium, potassium, chloride, urea, creatinine and plasma Ammonia. 2. Change in Quality of life measures from baseline to week 52 measured using the PedsQLTM Quality of Life Inventory questionnaires for parent and child completed at screening and at week 52 visit 3. Patient survival with a native liver measured using data collected from patient medical records at 52 weeks post-treatment 4. Patient survival with transplanted or native liver measured using data collected from patient medical records at 24 and 52 weeks post-treatment | — |
Countries
England, United Kingdom
Contacts
Public ContactAnil;Barath Dhawan;Jagadisan
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Outcome results
None listed