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

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: January 30, 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 up to twelve months in paediatric patients suffering from CN or UCD.


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:
  • Adverse events and serious adverse events related to infusion and concomitant treatment [ Time Frame: up to 6 month post infusion ] [ Designated as safety issue: Yes ]
    Assessed by physical exam, vital signs , Clinical Lab tests and Morphology of liver, bile ducts and portal system by ultrasound

  • Safety of the technical intervention [ Time Frame: During 6 months for four time windows ] [ Designated as safety issue: Yes ]
    Reactogenicity of infusion,short and mid term safety of infusion


Secondary Outcome Measures:
  • long-term safety profile of HepaStem for both indications [ Time Frame: up to 12 months post infusion ] [ Designated as safety issue: Yes ]
    Physical examination, Vital signs,Clinical laboratory tests of liver enzymes, renal function, coagulation factors, hematology,Level of anti-HLA and other auto-immune markers, Adverse events and serious adverse events related to infusion and concomitant treatments

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

Other Outcome Measures:
  • characterize the engraftment capacity of HHLAPC for both indications [ Time Frame: baseline, and 6 month (optional at 12 month FU ] [ Designated as safety issue: No ]
    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: November 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: April 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 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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.
  Contacts and Locations
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
Universitair Ziekenhuis (UZ) Gent
Gent, Belgium, 9000
France
CHU Bicêtre
Le Kremlin Bicêtre Cedex, France, 94275
Hôpital Jeanne de Flandre, CHRU Lille
Lille Cedex, France, 59037
Hôpital de la Timone, CHU de Marseille
Marseille, France, 13385
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: January 30, 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:
Crigler-Najjar Syndrome
Urea Cycle Disorders, Inborn
Cardiomyopathies
Hyperbilirubinemia, Hereditary
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 23, 2014