Study to Evaluate the Efficacy of HepaStem in Urea Cycle Disorders Paediatric Patients (HEP002)

Prospective, Open Label, Multicenter, Efficacy and Safety Study of Several Infusions of HepaStem in Urea Cycle Disorders Paediatric Patients

The aim of the study is to assess the efficacy of HepaStem treatment in paediatric patients suffering from urea cycle disorders.

Study Overview

• Status: Completed
• Conditions: Urea Cycle Disorders
• Intervention / Treatment: Biological: HepaStem

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
• France
  • Lille, France, 59037
    • Hôpital Jeanne de FLANDRE, CHRU LILLE
• Poland
  • Warszawa, Poland
    • Instytut - Pomnik Centrum Zdrowia Dziecka
• Spain
  • Badajoz, Spain, 06010
    • Hospital Materno Infatil de Badajoz
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron de Barcelona
  • Málaga, Spain, 29011
    • Hospital Materno Infantil de Málaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Paediatric patients < 12 years prior to infusion
• Patient presents with UCD
• Patient shows patency of the portal vein and branches, with normal flow velocity as confirmed by Doppler US and accessibility of the portal vein and /or affluants.

Main Exclusion Criteria:

• Patient has mild disease severity, easily controlled under standard of care therapy, with no recurrent metabolic crises.
• Patient is registered on a liver transplant waiting list or is scheduled for living donor liver transplantation before the end of the study.
• Patient presents acute liver failure.
• Patient presents clinical or radiological evidence of liver cirrhosis.
• Patient presents or has a history of hepatic or extrahepatic malignancy.
• Patient has a known clinically significant cardiac malformation.
• Patient has a personal history of venous thrombosis, or has a clinically significant abnormal value for protein S, protein C, anti-thrombin III, and /or activated Protein C Resistance (aPCR) at screening. In case of known family history, a complete coagulation work-up should be performed. In all above described cases, results need to be discussed with PB before enrolling the patient in the study.
• Patient had or has a renal insufficiency treated by dialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HepaStem; Target total dose 50x10E6 cells/kg	Biological: HepaStem; HepaStem will be administered in maximum 4 infusion days, spread over an 8-week period with an interval of 2 to 3 weeks between infusion days. The target total dose of cells will be 50x10E6 cells/kg body weight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy as determined by de novo ureagenesis (C13 tracer method)	at 6m post-first infusion day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as determined by de novo ureagenesis (C13 tracer method)		at 3, 9 and 12 months post-first infusion day
Efficacy as determined by Ammonia (NH3) values		up to 12 months post-first infusion day
Efficacy as determined by amino acids in plasma		up to 12 months post-first infusion day
Efficacy as determined by report of metabolic decompensations		up to 12 months post-first infusion day
Efficacy as determined by report on actual supportive treatment, adjustment of protein restriction and amino acids supplements		up to 12 months post-first infusion day
Efficacy as determined report on behavior, cognitive skills and health-related quality-of-life indicators		up to 12 months post-first infusion day
To evaluate the safety during the year following HepaStem infusions (composite)	Safety evaluation in terms of (1) clinical status, (2) portal vein hemodynamics, (3) morphology of the liver, bile ducts and portal system, (4) laboratory tests, (5) De novo detection of donor-specific circulating anti-human leukocyte antigen (HLA) antibodies, and/or other immune-related markers, (6) serious adverse events and clinically significant adverse events related to HepaStem, technical intervention, and concomitant treatments.	up to 12 months post-first infusion day

Collaborators and Investigators

• Sponsor: Promethera Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 3, 2015

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: UCD; cell therapy; stem cell; Urea Cycle Disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Disease; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: HEP002