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

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ClinicalTrials.gov Identifier: NCT01765283
Recruitment Status : Completed
First Posted : January 10, 2013
Last Update Posted : May 19, 2015
Sponsor:
Information provided by (Responsible Party):
Promethera Biosciences

Tracking Information
First Submitted Date  ICMJE January 9, 2013
First Posted Date  ICMJE January 10, 2013
Last Update Posted Date May 19, 2015
Study Start Date  ICMJE March 2012
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2014)
Safety of HepaStem in paediatric patients suffering from CN or UCD [ Time Frame: 6 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2013)
  • Adverse events and serious adverse events related to infusion and concomitant treatment [ Time Frame: up to 6 month post infusion ]
    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 ]
    Reactogenicity of infusion,short and mid term safety of infusion
Change History Complete list of historical versions of study NCT01765283 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2014)
  • Long-term safety profile of HepaStem in both indications [ Time Frame: From 6 to 12 months post-administration ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2013)
  • long-term safety profile of HepaStem for both indications [ Time Frame: up to 12 months post infusion ]
    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 ]
Current Other Pre-specified Outcome Measures
 (submitted: October 2, 2014)
To characterize the engraftment of HepaStem [ Time Frame: at 6 month, and optional at 12 month. ]
By liver biopsy, enzymatic activity (quantitative) on the biopsies or, donor sequences by RT PCR or in situ hybridisation (FISH) or immunohistochemistry.
Original Other Pre-specified Outcome Measures
 (submitted: January 9, 2013)
characterize the engraftment capacity of HHLAPC for both indications [ Time Frame: baseline, and 6 month (optional at 12 month FU ]
liver biopsy ,Enzymatic activity (quantitative) on the biopsies or, Donor sequences by RT PCR or in situ hybridisation (FISH) or immunohistochemistry.
 
Descriptive Information
Brief Title  ICMJE Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN)
Official Title  ICMJE 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.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Urea Cycle Disorders,
  • Crigler Najjar Syndrome
Intervention  ICMJE Biological: HepaStem
Other Name: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
Study Arms  ICMJE
  • Experimental: Hepastem Low dose
    12.5x106cells/kg
    Intervention: Biological: HepaStem
  • Experimental: Hepastem Intermediate dose
    50x106cells/kg
    Intervention: Biological: HepaStem
  • Experimental: Hepastem High dose
    200x106cells/kg
    Intervention: Biological: HepaStem
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 30, 2014)
20
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2013)
18
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Israel,   Italy,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01765283
Other Study ID Numbers  ICMJE HEP001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Promethera Biosciences
Study Sponsor  ICMJE Promethera Biosciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Promethera Biosciences
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP