Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN)

Urea Cycle Disorders Clinical Trial

— HEP001  

Official title:

A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Promethera HepaStem in Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) Paediatric Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01765283
• Other study ID #: HEP001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2012
• Est. completion date: April 2015

Study information

• Verified date: October 2020
• Source: Promethera Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and to appraise the efficacy of one cycle of Hepastem (Heterologous Human Adult Liver-derived Progenitor Cells, HHALPC) infusions in paediatric patients suffering from CN or UCD. The study duration: 12 months starting from the day of treatment: 6 months active surveillance and 6 months observation post-infusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

GENERAL:

1. Subject shows patency of the portal vein and branches, with normal flow velocity in the main portal vein 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. MAIN INCLUSION CRITERIA

Crigler-Najjar Syndrome specific:

• Patient presents with Crigler-Najjar syndrome type 1.
• 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:

• Diagnosis of one of the urea cycle disorders of which the disease is of such severity to warrant liver transplantation or alternatives despite full conservative therapy,
• subject experiencing serious impairment in quality of life despite full conservative therapy. MAIN EXCLUSION CRITERIA
• The subject is 18 years or older at time of screening.
• The subject presents acute liver failure, clinical or radiological evidence of liver fibrosis or cirrhosis, presents or has a history of hepatic or extrahepatic malignancy
• The patient has a non-corrected cardiac malformation, has a known medical or family history of coagulopathy, had or has a renal insufficiency treated by dialysis.
• The subject requires valproate therapy.
• The subject has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow.
• The subject has a porto systemic shunt or fistula assessed by Doppler US.
• Patients with disease of such severity that liver transplantation is an absolute indication.

Related Conditions & MeSH terms

• Cardiomyopathies
• Crigler Najjar Syndrome
• Crigler-Najjar Syndrome
• Syndrome
• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Intervention

Biological:
• HepaStem

Locations

Country	Name	City	State
Belgium	Saint Luc University Hospital	Brussels
Belgium	Universitair Ziekenhuis (UZ) Antwerpen	Edegem
France	CHU Bicêtre	Le Kremlin Bicêtre Cedex
France	Hôpital Jeanne de Flandre, CHRU Lille	Lille Cedex
France	Hôpital des Enfants, CHU de Toulouse	Toulouse cedex 9
Israel	Rambam Medical Center, Meyer Children's Hospital	Haifa
Israel	Hadassah Ein-Kerem Medical Center	Jerusalem
Israel	Schneider Children's Medical Center of israel	Petach Tikva
Italy	Ospedale Pediatrico Bambino Gesu di Roma	Roma
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Great Ormond Street Hospital London	London

Sponsors (1)

Lead Sponsor	Collaborator
Promethera Biosciences

Countries where clinical trial is conducted

Belgium,  France,  Israel,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To characterize the engraftment of HepaStem	By liver biopsy, enzymatic activity (quantitative) on the biopsies or, donor sequences by RT PCR or in situ hybridisation (FISH) or immunohistochemistry.	at 6 month, and optional at 12 month.
Primary	Safety of HepaStem in paediatric patients suffering from CN or UCD	Evaluation of the clinical status, portal-vein hemodynamics, morphology of the liver, de novo detection of circulating anti-HLA antibodies, and/or other immune related markers as well as Serious Adverse Events (SAEs) and clinically significant Adverse Events (AEs) related to infusion.	6 months
Secondary	Long-term safety profile of HepaStem in both indications	Assessment of reactogenicity and safety of the treatment during 6 to 12 months post infusion (long-term safety) is evaluated.	From 6 to 12 months post-administration
Secondary	Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts	UCD: 13C tracer test to measure ureagenesis, ammonium values, amino acids in plasma, neuropsychological assessment and quality of life indicators: (1) report on actual supportive treatment and any adjustment of diet (protein restriction (low protein diet) and amino acids supplements). (2) report on cognitive skills, behaviour, and health related quality of life effect).; CN: measure of the blood unconjugated bilirubin and serum total bilirubin levels and quality of life indicators: (1) adjustment of duration of phototherapy, (2) report on cognitive skills, behaviour, and (3) health related quality of life effect.	0-6 months, 6-12 months