Crigler-Najjar syndrome is associated with a complete or partial hepatic deficit of bilirubin glucuronosyltransferase activity and is apparent during the neonatal period by intense jaundice. The urea cycle disorders are inborn errors of metabolism that affect the transfer of nitrogen into urea. There are six disorders: N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase I deficiency, Ornithine transcarbamylase deficiency, citrullinemia, argininosuccinic aciduria and argininemia
Conditions
Sponsors
Promethera Biosciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) patients having received infusions of HepaStem during a former interventional clinical study conducted by PB and who have terminated their participation in that study. 2. For subject under 18 years of age (16 year in UK) and for adult subject legally incapable: subject (if capable of signing) and parents or legal representative have provided a written informed assent/consent before enrolment or For adult subject capable of signing: subject has provided a written informed assent/consent before enrolment. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has received mature liver cells, stem cells transplantation other than HepaStem, or organ liver transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to document the safety of HepaStem therapy during a period up to a maximum of 48 months (4 years (Y)) in the SAF001 study (SAF001 Y1+Y2+Y3+Y4). This long term safety follow-up study will start when the patient is ending the period of active surveillance post infusion of Hepastem in any former interventional study (Study A) conducted by Promethera Biosciences (PB). The safety will be assessed in terms of clinical status, biochemical parameters and morphology of the liver, detection of circulating anti-HLA antibodies specific for donor cells or other immune markers related to liver diseases as well as Serious Adverse Events (SAEs) and AEs of Special Interest (AESI) related to HepaStem therapy.;Secondary Objective: The secondary objectives are: - to document the long term disease evolution and efficacy of Hepastem up to a maximum of 24 months in the SAF001 study (SAF001 Y1+Y2) - to document the long term disease evolution and efficacy of Hepastem up to a maximum of 36 months post infusion (Study A Y1 + SAF001 Y1+Y2) - to document the long term disease evolution and efficacy of Hepastem up to a maximum of 60 months post infusion (Study A Y1 + SAF001 Y1+Y2+Y3+Y4). - to document the general safety during a period up to a maximum of 60 months post infusion (Study A Y1 + SAF001 Y1+Y2+Y3+Y4). ;Primary end point(s): The primary endpoint is to characterise the long term safety profile of HepaStem therapy. Assessment of safety will be achieved by evaluating the following parameters: - Physical examination - Vital signs - Biochemical parameters of liver function - Liver tumor marker - Autoimmune markers related to liver pathology - Anti-HLA antibodies specific for donor cell haplotypes - Morphology of liver, bile ducts and portal system by ultrasound - Non-serious or serious Adverse Events of Special Interest (AESIs, as defined in Section 12.1.2 of the protocol) and Serious Adverse Events (SAEs) related to HepaStem therapy ;Timepoi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are to characterize 1. the disease evolution, 2. the efficacy of HepaStem therapy and 3. to report on general safety. This assessment will be based on evaluation of: UCD condition: - Metabolic parameters - Ammonium (NH3) values - Amino acids in plasma: Alanine, Arginine, Citrulline, Glutamine - Urine: Orotic acid for OTC patients only; argininosuccinate acid only in ASL deficiency patients - Report on supportive treatment and any adjustment of: - Protein tolerance - Amino acids supplements - Nitrogen scavengers CN condition: - Metabolic parameters - Serum total bilirubin levels and unconjugated bilirubin levels - Report on actual supportive treatment and any adjustment of: - Duration of phototherapy - Phenobarbital treatment Both conditions: - Report on cognitive skills, behaviour, and health related quality of life indicators - Frequency and severity of metabolic decompensation (reported as AESIs) Assessment of safety will be done by evaluating non-serious or serious Adverse Events of Special Interest (AESIs, as defined in Section 12.1.2 of the protocol) and Serious Adverse Events (SAEs) related to concomitant medications or other causes. ;Timepoint(s) of evaluation of this end point: A 2-year assessment of safety, of disease evolution, and of efficacy of Hepastem will be done by scheduling visits every 6 months (+/- 1 month) for 2 years (years 1 and 2). An additional 2-year assessment of safety, of disease evolution and of efficacy of Hepastem will be done by scheduling yearly (+/- 1 month) visits for 2 years (years 3 and 4) and by scheduling a mid-year (phone) interview during years 3 and 4 (+/- 1 month). | — |
Countries
Belgium, Italy, Portugal, United Kingdom
Contacts
Public ContactVinciane Wouters
Promethera Biosciences
Outcome results
None listed