Urea Cycle DisordersPhase 1/2HEP001NCT01765283
Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN)
A Phase 1/2 study testing HepaStem in people with Urea Cycle Disorders and Crigler Najjar Syndrome, run by Cellaion SA at 11 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Urea Cycle Disorders, Crigler Najjar Syndrome
- What is being tested?
- HepaStem
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 11 sitesin 5 countries
- Study dates
- Mar 2012to Apr 2015
- Phase
- Phase 1/2
- 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 17 years
- All sexes
- No healthy volunteers
- Child
GENERAL:
- Subject shows patency of the portal vein and branches, with normal flow velocity in the main portal vein as confirmed by Doppler ultrasound and accessibility of the portal vein, or respectively, accessibility of the umbilical vein.
- Subject (if capable of signing) and parents or legal representative have provided a written informed assent/consent.
- Female subjects of childbearing potential need to have a negative pregnancy test and must agree to use an acceptable method of contraception throughout the study.
MAIN INCLUSION CRITERIA
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.
MAIN EXCLUSION CRITERIA
- 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.
Trial locations and contacts
11 sites in 5 countries.
11 sites in 5 countries
France3 sites
CHU Bicêtre
Le Kremlin-Bicêtre, 94275
Hôpital Jeanne de Flandre, CHRU Lille
Lille, 59037
Hôpital des Enfants, CHU de Toulouse
Toulouse, 31059
Israel3 sites
Rambam Medical Center, Meyer Children's Hospital
Haifa, 31096
Hadassah Ein-Kerem Medical Center
Jerusalem, 91240
Schneider Children's Medical Center of israel
Petah Tikva, 49202
Belgium2 sites
Saint Luc University Hospital
Brussels
Universitair Ziekenhuis (UZ) Antwerpen
Edegem, 2650
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham, B4 6NH
Great Ormond Street Hospital London
London, WC1N 3JH
About this study
Official title: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Promethera HepaStem in Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) Paediatric Patients.
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
- Being tested
- HepaStem
- Keywords
- CN,, UCD
- Medical subject headings
- Urea Cycle Disorders, Inborn, Crigler-Najjar Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HepaStemBiological
Also called HHALPC,Heterologous Human Adult Liver derived Progenitor Cells
| Study group | Role | What they receive |
|---|---|---|
| Hepastem Low dose | Experimental | 12.5x106cells/kg Receives: Biological: HepaStem |
| Hepastem Intermediate dose | Experimental | 50x106cells/kg Receives: Biological: HepaStem |
| Hepastem High dose | Experimental | 200x106cells/kg Receives: Biological: HepaStem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
Long-term safety profile of HepaStem in both indications
Assessment of reactogenicity and safety of the treatment during 6 to 12 months post infusion (long-term safety) is evaluated.
Measured: From 6 to 12 months post-administration
Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts
UCD: 13C tracer test to measure ureagenesis, ammonium values, amino acids in plasma, neuropsychological assessment and quality of life indicators: (1) report on actual supportive treatment and any adjustment of diet (protein restriction (low protein diet) and amino acids supplements). (2) report on cognitive skills, behaviour, and health related quality of life effect).
CN: measure of the blood unconjugated bilirubin and serum total bilirubin levels and quality of life indicators: (1) adjustment of duration of phototherapy, (2) report on cognitive skills, behaviour, and (3) health related quality of life effect.
Measured: 0-6 months, 6-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study startMar 2012
- Primary completionOct 2014
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cellaion SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765283
- Sponsor's protocol ID
- HEP001
- Acronym
- HEP001
- Status last verified
- Oct 2020
- First submitted
- 9 Jan 2013
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32028991
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Promethera HepaStem in Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) Paediatric Patients.
- ClinicalTrials.gov ID
- NCT01765283
- Acronym / sponsor ID
- HEP001 / HEP001
- Conditions
- Urea Cycle Disorders, Crigler Najjar Syndrome
- Keywords
- CN,, UCD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Cellaion SAIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hepastem Low dose | Experimental | Biological: HepaStem12.5x106cells/kg |
| Hepastem Intermediate dose | Experimental | Biological: HepaStem50x106cells/kg |
| Hepastem High dose | Experimental | Biological: HepaStem200x106cells/kg |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HepaStemAlso: HHALPC,Heterologous Human Adult Liver derived Progenitor Cells | Biological | Hepastem High dose, Hepastem Intermediate dose, Hepastem Low dose |
Primary outcome
Safety of HepaStem in paediatric patients suffering from CN or UCD
Time frame: 6 months
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.
2 secondary outcomes
Long-term safety profile of HepaStem in both indications
Time frame: From 6 to 12 months post-administration
Preliminary efficacy of HepaStem in both indications (CN and UCD) and for different weight cohorts
Time frame: 0-6 months, 6-12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Derived from this study: PubMed 32028991Coppin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HepaStem in people with Urea Cycle Disorders and Crigler Najjar Syndrome, run by Cellaion SA at 11 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France, Israel, Belgium, United Kingdom, Italy. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of HepaStem in paediatric patients suffering from CN or UCD (time frame: 6 months). 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 NCT01765283, which also lists 1 linked publication.
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 19 Oct 2020.