Clinical trial NCT01765283: Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Urea Cycle Disorders
Crigler Najjar Syndrome
Keywords: CN,
UCD
Lead sponsor: Cellaion SA
Sponsor class: INDUSTRY
First posted: 2013-01-10
Enrollment: 20
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety of HepaStem in paediatric patients suffering from CN or UCD
timeFrame: 6 months
Secondary outcomes:
measure: Long-term safety profile of HepaStem in both indications
timeFrame: From 6 to 12 months post-administration
measure: Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts
timeFrame: 0-6 months, 6-12 months
Other outcomes:
measure: To characterize the engraftment of HepaStem
timeFrame: at 6 month, and optional at 12 month.
Locations:
city: Brussels
country: Belgium
facility: Saint Luc University Hospital
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis (UZ) Antwerpen
city: Le Kremlin Bicêtre Cedex
country: France
facility: CHU Bicêtre
city: Lille Cedex
country: France
facility: Hôpital Jeanne de Flandre, CHRU Lille
city: Toulouse cedex 9
country: France
facility: Hôpital des Enfants, CHU de Toulouse
city: Haifa
country: Israel
facility: Rambam Medical Center, Meyer Children's Hospital
city: Jerusalem
country: Israel
facility: Hadassah Ein-Kerem Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of israel
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu di Roma
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital London
Study officials:
References:
citation: Coppin LCF, Smets F, Ambroise J, Sokal EEM, Stephenne X. Infusion-related thrombogenesis by liver-derived mesenchymal stem cells controlled by anticoagulant drugs in 11 patients with liver-based metabolic disorders. Stem Cell Res Ther. 2020 Feb 7;11(1):51. doi: 10.1186/s13287-020-1572-7.