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

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

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

Conditions
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Urea Cycle Disorders

Intervention / Treatment
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* Biological: HepaStem


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HepaStem<br>Target total dose 50x10E6 cells/kg | Biological: HepaStem<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urea Cycle Disorder, UCD, cell therapy, stem cell