A phase I/II trial for evaluating both safety and preliminary efficacy of one cycle of Promethera Hepastem in Urea Cycle Disorders and Crigler-Najjar Syndrome patients

• Conditions: Crigle-Najjar syndrome is associated with a complete or partial hepatic deficit of bilirubin glucoronosyltransferase 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 desorders: N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthase I deficiency, Ornithine transcarbamylase deficiency, citrullinemia, argininosuccinic aciduria and argininemia.; MedDRA version: 15.1Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolismSystem Organ Class: 100000004861; MedDRA version: 15.1Level: PTClassification code 10011386Term: Crigler-Najjar syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 15.1Level: SOCClassification code 10010331Term: Congenital, familial and genetic disordersSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 15.1Level: LLTClassification code 10021601Term: Inborn error of metabolism NOSSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2011-004074-28-IT
• Lead Sponsor: PROMETHERA BIOSCIENCES

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-14
• Last Update Posted: 19 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

General: 1. Subject shows patency of the portal vein and branches, with normal flow velocity in the main portal vein and normal portal vein pressure as confirmed by Doppler ultrasound and accessibility of the portal vein, or respectively, accessibility of the umbilical vein. 2. Subject (if capable of signing) and parents or legal representative have provided a written informed assent/consent. 3. Female subjects of childbearing potential need to have a negative pregnancy test and must agree to use an acceptable method of contraception throughout the study. Crigler-Najjar Syndrome specific: Patient presents with Crigler-Najjar syndrome type 1 and diagnosis must be confirmed by genetic mutation analysis if not available. 4. Patient presents with Crigler-Najjar syndrome type 2 - poorly controlled under phenobarbital treatment, or - experiencing serious impairment in quality of life. Diagnosis must be confirmed by genetic mutation analysis if not available. Urea Cycle Disorders specific : 5. Diagnosis of one of the urea cycle disorders (CPS I D, OCTD, ASSD, ASLD, Arginase deficiency, and NAGSD) - of which the disease is of such severity to warrant liver transplantation or alternatives despite full conservative therapy, or - subject experiencing serious impairment in quality of life despite full conservative therapy. Diagnosis must be confirmed by genetic mutation analysis if not available.
Are the trial subjects under 18? yes
Number of subjects for this age range: 18
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

1. The subject is 18 years or older at time of screening. 2. The subject presents acute liver failure. 3. The subject presents clinical or radiological evidence of liver fibrosis or cirrhosis 4. The subject presents or has a history of hepatic or extrahepatic malignancy 5. The patient has a non-corrected cardiac malformation. 6. The subject has a known medical or family history of coagulopathy. 7. The subject participates currently in another clinical trial – except disease registry and observational HepaStem study. 8. The subject underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant. 9. The subject has a contraindication to immunosuppressive therapy. 10. The subject has a known hypersensitivity or allergy to the recommended antibiotics to prevent post-operative infections according to institutional guidelines, and basiliximab, solumedrol or tacrolimus unless alternative drugs can be used without risk for the patient. 11. The subject has a known hypersensitivity or allergy to bivalirudin. 12. The subject had or has a renal insufficiency treated by dialysis. 13. The subject requires valproate therapy. 14. The subject has a known hypersensitivity or allergy to contrast agents that cannot be treated adequately. 15. The subject has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow. 16. The subject has a porto systemic shunt or fistula assessed by Doppler US. 17. For umbilical vein access: The subject has any contraindication for umbilical vein catheterization (eg omphalitis, peritonitis, necrotizing enterocolitis, etc) 18. Any significant condition which in the Investigator’s opinion may interfere with the subject’s optimal participation in the study. 19. Patients with disease of such severity that liver transplantation is an absolute indication. 20. Patients with mild disease severity, easily controlled under standard of care therapy with no recurrent metabolic crises.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified