Acute liver failure in paediatric patients MedDRA version: 20.1 Level: LLT Classification code 10049844 Term: Acute liver failure System Organ Class: 100000004871
Conditions
Interventions
Product Name: Alginate micro-beads containing hepatocytes and mesenchymal stromal cells
Product Code: HMB002
Pharmaceutical Form: Infusion
Sponsors
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I. Infant or child (male or female) under the age of 16 years at recruitment. II. Written informed consent obtained from a parent / legal guardian; III. 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 as described in Appendix 1b; IV. Willing and able to comply with the study visit schedule; Are the trial subjects under 18? yes Number of subjects for this age range: 17 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: I. Severe ascites causing high intra-abdominal pressure and / or respiratory compromise; II. Intra-abdominal sepsis suspected or proven; III. Clinical condition too unstable to tolerate procedure without compromise; IV. Proven pre-existing allergy or intolerance to alginate on medical history; V. Proven pre-existing allergy to gentamicin on medical history; VI. Intraperitoneal or intra-abdominal malignancy; VII. Adhesions or fistulae to anterior abdominal wall; VIII. Children who weigh in excess of 33kg IX. Pregnant or lactating patients (positive pregnancy test for females of child bearing potential at screening). X. 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 the duration of the study. *Females of child bearing potential are females who have experienced menarche and are not surgically sterilised (e.g. by tubal occlusion, hysterectomy, bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). ** Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly. Highly effective methods of contraception as per HMA / CTFG working group are combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, the preparation may be oral, intravaginal or transdermal; progesterone-only hormonal contraception associated with inhibition of ovulation which may be oral, injectable or implantable; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence through the trial study period; *** Sexual abstinence is considered to be highly effective method only if defined as refraining from heterosexual activity from the date of consent until the week 52 visit. The reliability of this method should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. XI. Male patients who are not willing to use an effective method of contraception (condom, vasectomy, sexual abstinence) for the duration of the study, when engaging in sexual activity with a female of childbearing potential; XII. Participation in concurrent therapeutic trial for ALF; XIII. Imminent liver transplantation expected within 12 hours of infusion; XIV. Total hepatectomy; XV. Dependent on Extracorporeal Membrane Oxygenation (ECMO); XVI. Previous liver transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, biological activity and tolerability of transplantation of a single dose of microbeads made from the optimum combination of peptide-alginate, mesenchymal stromal cells (MSCs) and hepatocytes to paediatric patients with acute liver failure;Secondary Objective: To establish proof of concept of the transplantation of microbeads made from the optimum combination of peptide-alginate, MSCs and hepatocytes. To inform sample size and confidence intervals to design a larger randomized clinical trial ;Primary end point(s): Safety: Moderate to severe adverse event occurrences due to product in 1st 52 weeks post procedure Tolerability: assessed by the proportion of initiated infusions where >80% of the infusion is received by the patient. Biological activity: Survival with native liver at 24 weeks post treatment.;Timepoint(s) of evaluation of this end point: At IMP administration and then at 24 and 52 weeks post treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blood marker levels including haematological, biochemical and coagulation baseline to 52 weeks post treatment. Quality of life measures Survival with native liver at 52 weeks post treatment Survival with transplanted or native liver at 24- and 52-weeks post treatment.;Timepoint(s) of evaluation of this end point: Throughout 52 week trial period | — |
Countries
United Kingdom
Contacts
Public ContactPaediatric Liver Research
King's College Hospital NHS Foundation Trust
Outcome results
None listed