The urea cycle disorders are inborn errors of metabolism that affect the transfer of nitrogen into urea. There are seven disorders to be investigated: carbamoylphosphate synthetase I deficiency [CPS ID], ornithine transcarbamylase deficiency [OTCD], argininosuccinic acid synthetase deficiency [ASSD], argininosuccinic acid lyase deficiency [ASLD], arginase deficiency [ARGD], N-acetylglutamate synthase deficiency [NAGSD], and citrine deficiency. MedDRA version: 18.0 Level: LLT Classification code
Conditions
Interventions
Product Name: HepaStem
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Heterologous Human Adult Liver-derived Progenitor Cells
Current Sponsor code: HHALPC
Concentration unit: milli
Sponsors
Promethera Biosciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient who meets all of the following inclusion criteria will be eligible for participation in the study: 1. The patient is a pediatric patient =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A patient who meets any of the following exclusion criteria will not be enrolled in the study: 1. The patient presents acute liver failure. 2. The patient presents clinical or radiological evidence of liver cirrhosis. 3. The patient presents or has a history of hepatic or extrahepatic malignancy. 4. The patient has a known clinically significant cardiac malformation. 5. The patient has a personal history of venous thrombosis, or has a clinically significant abnormal value for protein S, protein C, anti-thrombin III, and /or activated Protein C Resistance (aPCR) at screening. In case of known family history, a complete coagulation work-up should be performed. In all above described cases, results need to be discussed with PB before enrolling the patient in the study. 6. The patient participates currently in another clinical trial – except disease registry and observational HepaStem study. 7. The patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or received HepaStem infusion. 8. The patient has a contraindication to methylprednisolone, tacrolimus. 9. The patient has a known hypersensitivity or allergy to bivalirudin. 10. The patient has a known hypersensitivity or allergy to the antibiotics preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found. 11. The patient had or has a renal insufficiency treated by dialysis. 12. The patient requires valproate therapy. 13. The patient has a known hypersensitivity or allergy to contrast agents (if applicable) that cannot be treated adequately. 14. The patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow. 15. The patient has a porto systemic shunt or fistula assessed by Doppler US or an Arantius channel or portal hypertension. 16. The site where the catheter is intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures. 17. The patient has an ongoing infection or suffered from an infection in the last 2 weeks (including active EBV infection at screening). The patient may be enrolled after resolution of the infection. 18. There is any significant condition or disability that, in the Investigator’s opinion, may interfere with the patient’s optimal participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the functional efficacy of HepaStem at 6 months after initiation of infusion in terms of ureagenesis improvement based on a functional test (13C tracer method). A stopping rule is introduced as a particular measure to protect pediatric patients: If the positive benefit risk ratio for the study is confirmed after the first five patients having completed FU visit 3 (6 m post first infusion), the study will be continued. ;Secondary Objective: 1. To evaluate the efficacy of HepaStem in terms of functional, clinical, and biochemical parameters up to one year after initiation of HepaStem infusion. 2. To evaluate the safety of HepaStem up to one year after initiation of HepaStem infusion. ;Primary end point(s): Ureagenesis improvement at 6 month post first infusion day (FU visit 3): absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at FU visits 3 compared with baseline evaluations (measurements at BL visit 1, BL visit 2 and BL visit 3). The results of the first 5 patients will first be assessed. If the positive benefit risk ratio for the study is confirmed after the first five patients having completed FU visit 3 (6 m post first infusion), the study will be continued. ;Timepoint(s) of evaluation of this end point: Ureagenesis improvement at 6 month post first infusion day (FU visit 3): absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at FU visits 3 compared with baseline evaluations (measurements at BL visit 1, BL visit 2 and BL visit 3). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Functional parameters: at month 3, month 9 and month 12 post first infusion day (FU visits 1, 5, 7) 2. Clinical and biochemical parameters: Efficacy up to 12 months post-first infusion day 3. Individual medical assessment: clinical improvement will be evaluated on a complete file of each patient after 6 months and after 12 months of initiation of HepaStem administration. 4. The safety parameters will be assessed for 4 periods - Screening Period - Baseline period - Active Treatment Period Events will be evaluated according to time from catheter placement, time from the first infusion and time from the last infusion received. - Follow-up Period Events will be evaluated according to time from the first infusion and time from the last infusion received. ;Secondary end point(s): 1. Functional parameter Ureagenesis improvement at month 3, month 9 and month 12 post first infusion day (FU visits 1, 5, 7): absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at these visits compared with baseline evaluations (measurements at BL visit 1, BL visit 2 and BL visit). 2. Clinical and biochemical parameters: Efficacy up to 12 months post-first infusion day as compared to prior medical condition based on: - Chronic protein intake (total and natural protein, reported in mg/kg/day and reported as compared to WHO safe level for age) considering diet evaluations at study visits during baseline period and at scheduled study visits during the follow-up period. - Chronic nitrogen scavenger dose (mg/kg/day) considering reported doses at scheduled study visits during baseline period and at scheduled study visits during the follow-up period. - Blood ammonia considering values measured at scheduled study visits during screening and baseline periods and at scheduled study visits during the follow-up period. - Relevant blood amino acids considering values measured at scheduled study visits during the scre | — |
Countries
Belgium, France, Poland, Spain
Contacts
Public ContactVinciane Wouters
Promethera Biosciences
Outcome results
None listed