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

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 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:

Genetics Home Reference related topics: argininosuccinic aciduria citrullinemia Crigler-Najjar syndrome N-acetylglutamate synthase deficiency ornithine translocase deficiency succinic semialdehyde dehydrogenase deficiency

U.S. FDA Resources

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.

Estimated Enrollment:	18
Study Start Date:	November 2012
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Hepastem Low dose 12.5x106cells/kg	Biological: HepaStem Other Name: HHLAPC,Heterologous Human Adult Liver derived Progenitor Cells
Experimental: Hepastem Intermediate dose 50x106cells/kg	Biological: HepaStem Other Name: HHLAPC,Heterologous Human Adult Liver derived Progenitor Cells
Experimental: Hepastem High dose 200x106cells/kg	Biological: HepaStem Other Name: HHLAPC,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:

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.
Urea Cycle Disorders specific 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.

Exclusion Criteria:

The subject is 18 years or older at time of screening.
The subject presents acute liver failure.
The subject presents clinical or radiological evidence of liver fibrosis or cirrhosis
The subject presents or has a history of hepatic or extrahepatic malignancy The patient has a non-corrected cardiac malformation.
The subject has a known medical or family history of coagulopathy.
The subject underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant.
The subject has a contraindication to immunosuppressive therapy.
The subject has a known hypersensitivity or allergy to bivalirudin.
The subject 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.
The subject has any contraindication for umbilical vein catheterization

Contacts and Locations

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

Locations

Belgium
Saint Luc University Hospital	Recruiting
Brussels, Belgium
Contact: Froncoise SMET, Prof. 32 02 764 19 20 francoise.smets@uclouvain.be
Principal Investigator: Froncoise Smet, MD
Universitair Ziekenhuis (UZ) Antwerpen	Recruiting
Edegem, Belgium, 2650
Contact: François Eyskens, MD 32 3 821 3000 francois.eyskens@uza.be
Principal Investigator: François Eyskens, MD
Universitair Ziekenhuis (UZ) Gent	Recruiting
Gent, Belgium, 9000
Contact: Ruth De Bruyne, MD 32 9 332 39 66 Ruth.debruyne@ugent.be
Principal Investigator: Ruth De Bruyne, MD
Universitair Ziekenhuis (UZ) Leuven	Recruiting
Leuven, Belgium, 3000
Contact: Luc Régal, MD 32 16 34 38 20 luc.regal@uzleuven.be
Principal Investigator: Luc Régal, MD
France
CHU Bicêtre	Recruiting
Le Kremlin Bicêtre Cedex, France, 94275
Contact: Emmanuel Jacquemin, MD 00 33 1 45 21 31 68 / 37 86 emmanuel.jacquemin@bct.aphp.fr
Principal Investigator: Emmanuel Jacquemin, MD
Hôpital Jeanne de Flandre, CHRU Lille	Recruiting
Lille Cedex, France, 59037
Contact: Dries Dobbelaere, MD 00 33 3 20 44 41 49 dries.dobbelaere@chru-lille.fr
Principal Investigator: Dries Dobbelaere, MD
Hôpital de la Timone, CHU de Marseille	Recruiting
Marseille, France, 13385
Contact: Brigitte Chabrol, MD 00 33 4 91 38 68 06 bchabrol@ap-hm.fr
Principal Investigator: Brigitte Chabrol, MD
CHU Paris-Robert Debré	Recruiting
Paris, France, 75019
Contact: Hélène Ogier de Baulny, MD 00 33 1 40 03 57 07 helene.ogier@rdb.aphp.fr
Principal Investigator: Hélène Ogier de Baulny, MD
Hôpital des Enfants, CHU de Toulouse	Recruiting
Toulouse cedex 9, France, 31059
Contact: Pierre Broué, MD 00 33 5 34 55 85 66 broue.p@chu-toulouse.fr
Principal Investigator: Pierre Broué, MD
CHRU Tours	Recruiting
Tours, France, 37000
Contact: François Labarthe, MD 00 33 2 47 47 38 18 francois.labarthe@univ-tours.fr
Principal Investigator: François Labarthe, MD
Israel
E Wolfson Medical Center	Not yet recruiting
Holon, Israel
Contact: Tali Sagi, Prof. 972 3 5028458 asagie@post.tau.ac.il
Sub-Investigator: Tali Sagi, MD
United Kingdom
Birmingham Children's Hospital	Recruiting
Birmingham, United Kingdom, B4 6NH
Contact: Patrick McKiernan, MD 44 78 87 53 49 70 pat.mckiernan@bch.nhs.uk
Principal Investigator: Patrick McKiernan, MD
Great Ormond Street Hospital London	Recruiting
London, United Kingdom, WC1N 3JH
Contact: Paul Gissen, MD 44 20 78 13 83 31 Paul.Gissen@gosh.nhs.uk
Principal Investigator: Paul Gissen, MD

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 10, 2013
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 June 18, 2013