Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) (HEP001)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Promethera Biosciences
ClinicalTrials.gov Identifier:
NCT01765283
First received: January 9, 2013
Last updated: October 2, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Urea Cycle Disorders,
Crigler Najjar Syndrome
Biological: HepaStem
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Promethera Biosciences:

Primary Outcome Measures:
  • Safety of HepaStem in paediatric patients suffering from CN or UCD [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Long-term safety profile of HepaStem in both indications [ Time Frame: From 6 to 12 months post-administration ] [ Designated as safety issue: Yes ]
    Assessment of reactogenicity and safety of the treatment during 6 to 12 months post infusion (long-term safety) is evaluated.

  • Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts [ Time Frame: 0-6 months, 6-12 months ] [ Designated as safety issue: No ]

    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.



Other Outcome Measures:
  • To characterize the engraftment of HepaStem [ Time Frame: at 6 month, and optional at 12 month. ] [ Designated as safety issue: No ]
    By liver biopsy, enzymatic activity (quantitative) on the biopsies or, donor sequences by RT PCR or in situ hybridisation (FISH) or immunohistochemistry.


Enrollment: 20
Study Start Date: March 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hepastem Low dose
12.5x106cells/kg
Biological: HepaStem
Other Name: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
Experimental: Hepastem Intermediate dose
50x106cells/kg
Biological: HepaStem
Other Name: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
Experimental: Hepastem High dose
200x106cells/kg
Biological: HepaStem
Other Name: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765283

Locations
Belgium
Saint Luc University Hospital
Brussels, Belgium
Universitair Ziekenhuis (UZ) Antwerpen
Edegem, Belgium, 2650
France
CHU Bicêtre
Le Kremlin Bicêtre Cedex, France, 94275
Hôpital Jeanne de Flandre, CHRU Lille
Lille Cedex, France, 59037
Hôpital des Enfants, CHU de Toulouse
Toulouse cedex 9, France, 31059
Israel
Rambam Medical Center, Meyer Children's Hospital
Haifa, Israel, 31096
Hadassah Ein-Kerem Medical Center
Jerusalem, Israel, 91240
Schneider Children's Medical Center of israel
Petach Tikva, Israel, 49202
Italy
Ospedale Pediatrico Bambino Gesu di Roma
Roma, Italy, 00165
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom, B4 6NH
Great Ormond Street Hospital London
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Promethera Biosciences
  More Information

No publications provided

Responsible Party: Promethera Biosciences
ClinicalTrials.gov Identifier: NCT01765283     History of Changes
Other Study ID Numbers: HEP001
Study First Received: January 9, 2013
Last Updated: October 2, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: Istituto Superiore di Sanità
Israel: Ministry of Health

Keywords provided by Promethera Biosciences:
CN,
UCD

Additional relevant MeSH terms:
Cardiomyopathies
Crigler-Najjar Syndrome
Disease
Syndrome
Urea Cycle Disorders, Inborn
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Cardiovascular Diseases
Central Nervous System Diseases
Genetic Diseases, Inborn
Heart Diseases
Hyperbilirubinemia, Hereditary
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014