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

NCT01765283 | Completed Phase 1 DMC

• 1 other identifier: HEP001
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 11

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.

Conditions

Urea Cycle Disorders; Crigler Najjar Syndrome

Keywords

CN,; UCD

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (2)

• Long-term safety profile of HepaStem in both indications

  From 6 to 12 months post-administration

• Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts

  0-6 months, 6-12 months

Other Outcomes (1)

• To characterize the engraftment of HepaStem

  at 6 month, and optional at 12 month.

Study Arms (3)

Hepastem Low dose

EXPERIMENTAL

12.5x106cells/kg

Biological: HepaStem

Hepastem Intermediate dose

EXPERIMENTAL

50x106cells/kg

Biological: HepaStem

Hepastem High dose

EXPERIMENTAL

200x106cells/kg

Biological: HepaStem

Interventions

HepaStem BIOLOGICAL

Also known as: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells

Hepastem High dose; Hepastem Intermediate dose; Hepastem Low dose

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cellaion SA: lead

Study Sites (11)

Saint Luc University Hospital

Brussels, Belgium

Location

Universitair Ziekenhuis (UZ) Antwerpen

Edegem, 2650, Belgium

Location

CHU Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Jeanne de Flandre, CHRU Lille

Lille, 59037, France

Location

Hôpital des Enfants, CHU de Toulouse

Toulouse, 31059, France

Location

Rambam Medical Center, Meyer Children's Hospital

Haifa, 31096, Israel

Location

Hadassah Ein-Kerem Medical Center

Jerusalem, 91240, Israel

Location

Schneider Children's Medical Center of israel

Petah Tikva, 49202, Israel

Location

Ospedale Pediatrico Bambino Gesu di Roma

Roma, 00165, Italy

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Great Ormond Street Hospital London

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32028991 DERIVED

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Crigler-Najjar Syndrome

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperbilirubinemia, Hereditary

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 10, 2013
• Study Start: March 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: April 1, 2015
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

FR (3); IT (1); BE (2); GB (2); IL (3)