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

October 13, 2020 updated by: Promethera Therapeutics

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Hepastem Low dose
12.5x106cells/kg
Biological: HepaStem
Other Names:
  • HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
EXPERIMENTAL: Hepastem Intermediate dose
50x106cells/kg
Biological: HepaStem
Other Names:
  • HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
EXPERIMENTAL: Hepastem High dose
200x106cells/kg
Biological: HepaStem
Other Names:
  • HHALPC,Heterologous Human Adult Liver derived Progenitor Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From 6 to 12 months post-administration
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.
0-6 months, 6-12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
at 6 month, and optional at 12 month.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Promethera Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (ACTUAL)

October 1, 2014

Study Completion (ACTUAL)

April 1, 2015

Study Registration Dates

First Submitted

January 9, 2013

First Submitted That Met QC Criteria

January 9, 2013

First Posted (ESTIMATE)

January 10, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HEP001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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