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

Primary Purpose

Urea Cycle Disorders, Crigler Najjar Syndrome

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
HepaStem
Sponsored by
Cellaion SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urea Cycle Disorders focused on measuring CN,, UCD

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Saint Luc University Hospital
  • Universitair Ziekenhuis (UZ) Antwerpen
  • CHU Bicêtre
  • Hôpital Jeanne de Flandre, CHRU Lille
  • Hôpital des Enfants, CHU de Toulouse
  • Rambam Medical Center, Meyer Children's Hospital
  • Hadassah Ein-Kerem Medical Center
  • Schneider Children's Medical Center of israel
  • Ospedale Pediatrico Bambino Gesu di Roma
  • Birmingham Children's Hospital
  • Great Ormond Street Hospital London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Hepastem Low dose

Hepastem Intermediate dose

Hepastem High dose

Arm Description

12.5x106cells/kg

50x106cells/kg

200x106cells/kg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
January 9, 2013
Last Updated
October 13, 2020
Sponsor
Cellaion SA
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1. Study Identification

Unique Protocol Identification Number
NCT01765283
Brief Title
Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN)
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cellaion SA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urea Cycle Disorders, Crigler Najjar Syndrome
Keywords
CN,, UCD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hepastem Low dose
Arm Type
Experimental
Arm Description
12.5x106cells/kg
Arm Title
Hepastem Intermediate dose
Arm Type
Experimental
Arm Description
50x106cells/kg
Arm Title
Hepastem High dose
Arm Type
Experimental
Arm Description
200x106cells/kg
Intervention Type
Biological
Intervention Name(s)
HepaStem
Other Intervention Name(s)
HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
Primary Outcome Measure Information:
Title
Safety of HepaStem in paediatric patients suffering from CN or UCD
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Long-term safety profile of HepaStem in both indications
Description
Assessment of reactogenicity and safety of the treatment during 6 to 12 months post infusion (long-term safety) is evaluated.
Time Frame
From 6 to 12 months post-administration
Title
Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts
Description
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.
Time Frame
0-6 months, 6-12 months
Other Pre-specified Outcome Measures:
Title
To characterize the engraftment of HepaStem
Description
By liver biopsy, enzymatic activity (quantitative) on the biopsies or, donor sequences by RT PCR or in situ hybridisation (FISH) or immunohistochemistry.
Time Frame
at 6 month, and optional at 12 month.

10. Eligibility

Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
GENERAL: 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. Subject (if capable of signing) and parents or legal representative have provided a written informed assent/consent. 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.
Facility Information:
Facility Name
Saint Luc University Hospital
City
Brussels
Country
Belgium
Facility Name
Universitair Ziekenhuis (UZ) Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
CHU Bicêtre
City
Le Kremlin Bicêtre Cedex
ZIP/Postal Code
94275
Country
France
Facility Name
Hôpital Jeanne de Flandre, CHRU Lille
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital des Enfants, CHU de Toulouse
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Rambam Medical Center, Meyer Children's Hospital
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Hadassah Ein-Kerem Medical Center
City
Jerusalem
ZIP/Postal Code
91240
Country
Israel
Facility Name
Schneider Children's Medical Center of israel
City
Petach Tikva
ZIP/Postal Code
49202
Country
Israel
Facility Name
Ospedale Pediatrico Bambino Gesu di Roma
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Great Ormond Street Hospital London
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32028991
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.
Results Reference
derived

Learn more about this trial

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

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