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

Primary Purpose

Urea Cycle Disorder

Status

Withdrawn

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

HepaStem Infusion

About this trial

This is an interventional treatment trial for Urea Cycle Disorder focused on measuring Urea Cycle Disorder, Hyperammonemia, Metabolic Decompensation

Eligibility Criteria

undefined - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
The site where the catheter is intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures.
The patient has an ongoing infection or suffered from an infection in the last 2 weeks (including active EBV infection at screening). The patient may be enrolled after resolution of the infection.
There is any significant condition or disability that, in the investigator's opinion, may interfere with the patient's participation in the study.

Sites / Locations

Samsung Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HepaStem Infusion

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Hemodynamics (measurement of portal vein pressures)

Safety evaluation in terms of portal-vein hemodynamics

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

Number of subjects with SAEs and AEs

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

Secondary Outcome Measures

Change of ureagenesis

Change of de novo ureagenesis at 3, 9 and 12 months after the first infusion: absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at FU visit 1, 5 and 7 compared with baseline evaluations.

Change of chronic protein intake

Chronic protein intake (total and natural protein, reported in mg/kg/day and reported as compared to WHO safe level for age) considering diet evaluations at study visits during baseline period and at scheduled study visits during the follow-up period.

Change of chronic nitrogen scavenger dose

Chronic nitrogen scavenger dose (mg/kg/day) considering reported doses at scheduled study visits during baseline period and at scheduled study visits during the follow-up period.

Change of the level of blood ammonia

Blood ammonia considering values measured at scheduled study visits during screening and baseline periods ant at scheduled study visits during the follow-up period.

Change of relevant blood amino acids values

Relevant blood amino acids considering values measured at scheduled study visits during the screening and baseline periods and at scheduled study visits during the follow-up period.

Number of subjects with Metabolic decompensations

Metabolic decompensations (hyperammonemia episodes with evocative symptomatology such as drowsiness, gastrointestinal symptoms and treated at hospital), considering all collected events during screening and baseline periods, during active treatment period, during follow-up period.

Change of chronic single amino acid intake

Chronic single animo acid intake considering reported doses at study visits during baseline period and at study visits during the follow-up period.

Evaluation of cognitive skill

Change of patient's cognitive skill score between the baseline period (at Baseline visit 1) and the follow-up period (at Follow up visit 7) will be evaluated by the Bayley Scales of Infant Development. (7 classes, from extremely low to very superior)

Evaluation of Behavior indicator

Behavior indicator will be evaluated by the Child Behavior Checklist (CBCL) at Baseline visit 1, during follow-up period at 4.5 months, 7.5 months and 12 months post-first fusion (at Follow up visit 2, 4, 7)

Evaluation of health-related Quality of Life (QoL) indicator

Health-related QoL indicator will be evaluated by the Pediatric Quality of Life Inventory at Baseline visit 1, during follow-up period at 4.5 months, 7.5 months and 12 months post-first fusion (at Follow up visit 2, 4, 7)

Full Information

NCT ID

NCT03884959

First Posted

March 3, 2019

Last Updated

November 4, 2020

Sponsor

HLB Cell Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03884959

Brief Title

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

Official Title

A Prospective, Open Label, Safety and Efficacy Study of Infusions of HepaStem in Urea Cycle Disorders Pediatric Patients

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor decided to stop enrollment

Study Start Date

July 12, 2018 (Actual)

Primary Completion Date

November 4, 2020 (Actual)

Study Completion Date

November 4, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

HLB Cell Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

Patient eligibility will be assessed during the Screening visit. The investigator should ensure that the chronic metabolic treatment (i.e. balance between low protein diet, supplements in amino acid mix, nitrogen scavenger and supplements in arginine and/or citrulline) of the patient is optimized for his/her metabolic condition. During the baseline period, 3 study visits will take place at 6 weeks interval for assessing the metabolic condition and the chronic metabolic treatment of the patient. 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. The follow-up period will start approximately 12 weeks after the first HepaStem infusion day. This period will last approximately 9 months. Study visits will take place every 1.5month, FU visit 1 to FU visit 7. Primary Objective: To demonstrate the functional efficacy of HepaStem at 6 months after initiation of infusion in terms of ureagenesis improvement based on a functional test (13C tracer method) To evaluate the safety of Hepastem up to one year after initiation the Hepastem infusion Secondary Objective: 1. To evaluate the efficacy of Hepastem in terms of functional, clinical, and biochemical parameters up to one year after initiation of the infusion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urea Cycle Disorder

Keywords

Urea Cycle Disorder, Hyperammonemia, Metabolic Decompensation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This is a single group, open label study

Masking

None (Open Label)

Masking Description

No Masking applied.

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HepaStem Infusion

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

HepaStem Infusion

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change of ureagenesis

Description

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.

Time Frame

at 6 months after the first infusion

Title

Hemodynamics (measurement of portal vein pressures)

Description

Safety evaluation in terms of portal-vein hemodynamics

Time Frame

up to 12 months after the first infusion

Title

Number of subjects with anti-HLA antibody

Description

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

Time Frame

up to 12 months after the first infusion

Title

Number of subjects with SAEs and AEs

Description

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

Time Frame

up to 12 months after the first infusion

Secondary Outcome Measure Information:

Title

Change of ureagenesis

Description

Time Frame

at 3, 9 and 12 months after the first infusion

Title

Change of chronic protein intake

Description

Time Frame