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Urea Cycle DisorderPhase 2NCT03884959

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

A Phase 2 study testing HepaStem Infusion in people with Urea Cycle Disorder, run by HLB Cell Co., Ltd. at 1 site in South Korea.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 12 years
Conditions the study is for
Urea Cycle Disorder
What is being tested?
HepaStem Infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteSouth Korea
Study dates
12 Jul 2018to 4 Nov 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 12 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

About this study

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

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.

Read the 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:

  1. 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)
  2. 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.
Being tested
HepaStem Infusion
Keywords
Urea Cycle Disorder, Hyperammonemia, Metabolic Decompensation
Medical subject headings
Urea Cycle Disorders, Inborn, Hyperammonemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HepaStem InfusionBiological

    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.

Study groups in NCT03884959
Study groupRoleWhat they receive
HepaStem InfusionExperimentalA 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.
Receives: Biological: HepaStem Infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: at 6 months after the first infusion

  2. Hemodynamics (measurement of portal vein pressures)

    Safety evaluation in terms of portal-vein hemodynamics

    Measured: up to 12 months after the first infusion

  3. 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

    Measured: up to 12 months after the first infusion

  4. Number of subjects with SAEs and AEs

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

    Measured: up to 12 months after the first infusion

Secondary outcomes (10)

  1. 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.

    Measured: at 3, 9 and 12 months after the first infusion

  2. 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.

    Measured: Up to 12 months after the first infusion

  3. 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.

    Measured: Up to 12 months after the first infusion

  4. 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.

    Measured: Up to 12 months after the first infusion

  5. 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.

    Measured: Up to 12 months after the first infusion

  6. 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.

    Measured: Up to 12 months after the first infusion

  7. 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.

    Measured: Up to 12 months after the first infusion

  8. 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)

    Measured: Up to 12 months after the first infusion

  9. 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)

    Measured: Up to 12 months after the first infusion

  10. 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)

    Measured: Up to 12 months after the first infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2019
  2. Study start12 Jul 2018
  3. Primary completion4 Nov 2020
  4. Study completion4 Nov 2020

Why it stopped: Sponsor decided to stop enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single group, open label study
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03884959
Sponsor's protocol ID
HEP002KR
Status last verified
Feb 2020
First submitted
3 Mar 2019
Last updated
6 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HepaStem Infusion in people with Urea Cycle Disorder, run by HLB Cell Co., Ltd. at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of ureagenesis (time frame: at 6 months after the first infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03884959.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2020.

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