A Safety and Efficacy Study of Infusions of HepaStem in Urea Cycle Disorders Pediatric Patients

NCT03884959 | Withdrawn Phase 2

• 1 other identifier: HEP002KR
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase2, prospective, open label study designed to investigate the safety and efficacy of several infusions of HepaStem. This study will include 5 pediatric Urea Cycle Disorder (UCD) patients under 12 years old. Its assessment includes all safety parameters and an efficacy assessment based on 13C tracer tests, ammonia, medication and diet changes. HepaStem will be administered in addition to the conventional UCD treatments.

Conditions

Urea Cycle Disorder

Keywords

Urea Cycle Disorder; Hyperammonemia; Metabolic Decompensation

Outcome Measures

Primary Outcomes (4)

• Change of ureagenesis

  Change of de novo ureagenesis at 6 months after the first infusion: absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at FU visit 3 compared with baseline evaluations.

  at 6 months after the first infusion

• Hemodynamics (measurement of portal vein pressures)

  Safety evaluation in terms of portal-vein hemodynamics

  up to 12 months after the first infusion

• Number of subjects with anti-HLA antibody

  Safety evaluation in terms of de novo detection of donor-specific circulating anti-HLA antibodies and/or other immune-related markers

  up to 12 months after the first infusion

• Number of subjects with SAEs and AEs

  Safety evaluations in terms of SAEs and clinically significant AEs related to study procedures

  up to 12 months after the first infusion

Secondary Outcomes (10)

• Change of ureagenesis

  at 3, 9 and 12 months after the first infusion

• Change of chronic protein intake

  Up to 12 months after the first infusion

• Change of chronic nitrogen scavenger dose

  Up to 12 months after the first infusion

• Change of the level of blood ammonia

  Up to 12 months after the first infusion

• Change of relevant blood amino acids values

  Up to 12 months after the first infusion

Study Arms (1)

HepaStem Infusion

EXPERIMENTAL

A calculated dose based on patient's body weight will be administered via Permanent mesenteric Portal Access and Catheter for four times or a Transient Percutaneous Transhepatic Catheter for three times.

Biological: HepaStem Infusion

Interventions

HepaStem Infusion BIOLOGICAL

HepaStem will be infused intravenously into the portal vein, either (1) via a permanent mesenteric PAC inserted surgically in an affluent of the portal vein; or (2) through a transient percutaneous transhepatic catheter inserted in to the portal vein under radio guidance.

HepaStem Infusion

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The patient is a pediatric patient \<12 years
• The patients presents with one of the following UCDs. (CPS1D, OTCD, ASSD, ASLD, ARGD)
• The patient has severe disease with impaired protein tolerance defined as: chronic protein restricted diet AND chronic treatment with at lease one nitrogen scavenger.
• The patient shows patency of the portal vein and its branches including mesenteric veins, with normal flow velocity as confirmed by Doppler US and accessibility of the portal vein and/or affluents.
• The patient (if capable of signing) and parents or legal representative have signed a written informed consent form.

You may not qualify if:

• The patient presents acute liver failure.
• The patient presents clinical or radiological evidence of liver cirrhosis.
• The patient presents or has a history of hepatic or extrahepatic malignancy.
• The patient has a known clinically significant cardiac malformation.
• The 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 sponsor before enrolling the patient in the study.
• Patient currently receiving other unapproved investigational drug or device.
• The patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or received HepaStem infusion.
• The patient has a contraindication to methylprednisolone, tacrolimus.
• The patient has a known hypersensitivity or allergy to heparin.
• The patient has a known hypersensitivity or allergy to the antibiotics preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found.
• The patient had or has a renal insufficiency treated by dialysis.
• The patient requires valproate therapy.
• The patient has a known hypersensitivity or allergy to contrast agents (if applicable) that cannot be treated adequately.
• The patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow.
• The patient has a porto systemic shunt or fistula assessed by Doppler US or an Arantius channel or protal hypertension.

Sponsors & Collaborators

• HLB Cell Co., Ltd.: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Hyperammonemia

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sanghoon Lee, MD. Ph.D

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No Masking applied.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single group, open label study

Study Record Dates

• First Submitted: March 3, 2019
• First Posted: March 21, 2019
• Study Start: July 12, 2018
• Primary Completion: November 4, 2020
• Study Completion: November 4, 2020
• Last Updated: November 6, 2020

Record last verified: 2020-02

Locations

KR (1)