neonatal hyperammonemic encephalopathy associated with inborn liver metabolic diseases MedDRA version: 14.1 Level: PT Classification code 10059521 Term: Methylmalonic aciduria System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: PT Classification code 10058299 Term: Argininosuccinate lyase deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: PT Classification code 10052450 Term: Ornith
Conditions
Interventions
Product Name: Human Liver Stem Cells (HLSCs)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: NA
Other descriptive name: Heterologous human adult liver-derived stem cells
Concentrati
Sponsors
AZIENDA SANITARIA OSPEDALIERA O.I.R.M. - S. ANNA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: neonatal-onset hyperammonemic encephalopathy; formal biochemical diagnosis of one of the five inborn metabolic diseases, as listed in the Table 1; formal evaluation for early liver transplantation; being referred to the Presidio Ospedaliero Infantile Regina Margherita, Centro delle Malattie Metaboliche, Torino, Italy; Are the trial subjects under 18? yes Number of subjects for this age range: 3 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: Refusal of signing the specific informed consent for entering the study; Evidence of uncontrolled coagulopathy;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate hepatic and extra-hepatic complications after liver intraparenchymal HLSC injection in neonates suffering from inborn liver metabolic diseases causing life-threatening neonatal-onset of hyperammonemic encephalopathy;Secondary Objective: To evaluate plasma ammonia levels ( 20 times normal, clinical and biochemical signs of liver failure (ascites, development of jaundice with conjugated bilirubin above 3 mg/dL, alterations in INR > 2.5), appearance of cancer-like liver nodular lesions. Extra-hepatic complications: pulmonary embolism, significant extra-hepatic (abdominal and/or chest) haemorrhage (requiring blood transfusion and / or specific treatment), documented sepsis with bacteremia, adverse reactions to sedative drugs administered for interventional radiological procedure. ;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated daily by monitoring adverse events, in the 15 days following the treatment. Other safety parameters will be evaluated weekly. A Safety Follow-up visit is planned, 4 weeks after last dose administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): to evaluate plasma ammonia levels (< 100 µmol/l following the treatment); to evaluate the daily protein intake, maintaining plasma ammonia levels < 100 µmol/l (measure: quantification of daily protein tolerance increase (g/kg/day) following the treatment); to reduce clinically significant hyperammonemic episodes (measure: number of hyperammonemic episodes following the treatment); to defer the time of liver transplantation from the scheduled time (measure: difference in months between the age at liver transplantation following the treatment and the age previously scheduled);Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated weekly and at the Safety Follow-up visit, 4 weeks after administration of last dose | — |
Countries
Italy
Contacts
Public ContactDr. Marco Spada
Centro Malattie Metaboliche/ Presidio Ospedaliero Regina Margherita
Outcome results
None listed