15N ammonium chloride ureagenesis validation clinical trial

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2021-000824-36-IT
• Date of registration: 16/08/2021
• Prospective Registration: Yes
• Primary sponsor: Unicyte AG
• Public title: 15N ammonium chloride ureagenesis validation clinical trial
• Scientific title: An open-label, controlled, multi-site, Phase I clinical trial to assess the ureagenesis capacity in newborns and infants up to the age of 12 months with neonatal and infantile onset of urea cycle disorders (UCD) using a 15N ammonium chloride tracer compared to newborns and infants without UCD. - reLiver-1
• Date of first enrolment: 04/04/2022
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000824-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Subjects without a diagnosis or suspicion of UCD will be enrolled in this trial as control subjects Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czechia, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom

Contacts

• Name: CEO
• Affiliation: Unicyte AG

• Name: CEO
• Affiliation: Unicyte AG

Key inclusion & exclusion criteria

Inclusion criteria:
A subject must meet ALL of the following criteria at Screening to be
eligible for this trial, with the exception of criteria 1 and 2 which do not
apply to subjects without UCD and criterium 3 that only applies for
subjects without UCD

Only for subjects with UCD
1. Subject has a genetically confirmed diagnosis of any of the following
urea cycle disorders: ASS, CPS1, ASL, OTC. Note: All subjects should
have genotyping information available, however if an exact genetic
diagnosis is not available, diagnosis of the UCD sub-type may be
confirmed by well accepted biochemical parameters
2. Subject has neonatal or infantile onset of UCD signs and symptoms
within the first 12 months of life; or subjects who have a family history
of UCD and are asymptomatic after birth due to a therapeutic regimen
started directly after birth;
Only for subjects without UCD
3. Subjects without UCD can have other stable illness that does not
interfere with the clinical trial according to the investigator judgement;
For all subjects (with and without UCD)
4. Male and female subjects aged up to 12 months, inclusive;
5. Subject has a body weight within the 5-95 percentile of the
corresponding age according to the WHO Child Growth Standards 2006;
6. Subject has stable clinical conditions (any acute condition needs to
be stabilised/treated before inclusion);
7. The parent(s) / legal representative(s) agrees that the subject will
not participate in any interventional clinical trial with an investigational
drug suspected of having an interaction with the urea cycle or 15NH4Cl
diagnostic tracer for the duration of the trial until the final follow-up
telephone call;
8. Ability and willingness of the parent(s) / legal representative(s) to
comply with the protocol requirements, including ability to bring the
subject to the scheduled trial visits;
9. Written informed consent by the parent(s) / legal representative(s)
of the subj
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
A subject must meet NONE of the following criteria at Screening to be
eligible for this trial, with the exception of criterion 1 which does not
apply to subjects with UCD:
Only for subjects with UCD
1. Subject has any suspected UCD of any sub-type. Note: subjects
suspected of having a UCD of any sub-type, but without either
confirmatory genotyping information or a typical biochemical diagnostic
pattern for any UCD gene defect, will not be enrolled in this trial.
For all subjects (with and without UCD)
2. Subject is a premature neonate (up to 37 gestation weeks not
completed);
3. Subject is in a period of significant post-natal weight drop based on
the judgement of the investigator ;
4. Subject has received any investigational compound within 30 days
(or 5 half-lives, whichever is longer) prior to first dose of diagnostic
tracer and according to the investigator judgement could interfere with
the clinical trial;
5. Subject has any other acute severe / other genetic / life limiting
disorder that would interfere with ethical and/or medical standards in
the conduct or follow up of the trial.
6. Subject has acute liver failure, clinical or radiological evidence of
liver fibrosis or cirrhosis, or presents a hepatic or extrahepatic
malignancy


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subject has a genetically confirmed diagnosis of any of the following urea cycle disorders: ASS, CPS1, ASL, OTC Subjects without UCD can have other stable illness that not interfere with the clinical trial according to the investigator judgement
MedDRA version: 20.1 Level: PT Classification code 10080020 Term: Urea cycle disorder System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: 15N ammonium chloride (15NH4Cl)
Product Code: [na]
Pharmaceutical Form: Tablet and powder for oral solution
INN or Proposed INN: Ammonium (15N) chloride
CAS Number: 39466-62-1
Current Sponsor code: Ammonium (15N) chloride
Other descriptive name: Ammonium (15N) chloride
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Primary end point(s): The intra-subject inter-occasion variability of the [15N] urea
enrichment area under the plasma concentration-time curve over 2
hours (AUC0-2) following up to 4 15NH4Cl diagnostic tracer
administrations over a 36-week period to subjects with neonatal-onset
UCD.

Secondary Objective: To assess the intra-subject inter-occasion
variability of ureagenesis in infants with a confirmed diagnosis of UCD
over a period of up to 36 weeks using a 15NH4Cl diagnostic tracer. •To
assess disease stability in neonates and infants with a confirmed
diagnosis of UCD over a period of up to 36 weeks.
Secondary Objcs: •To assess the ureagenesis and its variability in
neonates and infants without UCD over a period of 12 weeks using a
15NH4Cl diagnostic tracer. •To compare the inter-subject variability and
extent of impairment of ureagenesis in subjects with UCD with the
ureagenesis capacity in neonates and infants without UCD using a
15NH4Cl diagnostic tracer. •To correlate the ureagenesis, in both
subjects with and without UCD, as determined by the 15NH4Cl tracer
assay, with blood levels of ammonia, citrulline and glutamine
Safety Objectives: To assess the safety and tolerability of 15NH4Cl
diagnostic tracer in neonates and infants with and without UCD.

Main Objective: To assess the intra-subject inter-occasion variability of ureagenesis inneonates with a confirmed diagnosis of UCD over a period of up to 36 weeks using a 15NH4Cl diagnostic tracer.

Timepoint(s) of evaluation of this end point: Over a 36-week period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: According to the protocol

Secondary end point(s): The intra-subject inter-occasion variability of the [15N] urea
enrichment area under the plasma concentration-time curve over 2
hours (AUC0-2) following up to 4 15NH4Cl diagnostic tracer
administrations over a 36-week period to subjects with infantile-onset
UCD.
•The number of subjects with UCD demonstrating stable disease at
Weeks 0, 12, 24 and 36.
•The blood concentrations of ammonia, glutamine and citrulline up to 2
hours following
o up to 4 15NH4Cl diagnostic tracer administrations to subjects with
UCD (Weeks 0, 12, 24 and 36).
o up to 2 15NH4Cl diagnostic tracer administrations to subjects without
UCD (Weeks 0 and 12).
•The number of hyperammonaemia events and crises experienced since
the previous trial visit at Weeks 12, 24 and 36 (subjects with UCD only).
•The number of subjects following a stable protein diet, with no
unplanned adjustments since the previous trial visit, at Weeks 12, 24
and 36 (subjects with UCD only).
Secondary Endpoints:
•The intra-subject inter-occasion variability of the [15N] urea
enrichment area under the plasma concentration-time curve over 2
hours (AUC0-2) following
o up to 4 15NH4Cl diagnostic tracer administrations over a 36-week
period to subjects with infantile-onset UCD.
o up to 2 15NH4Cl diagnostic tracer administrations over a 12-week
period to subjects without UCD.
•The inter-subject variance of the [15N] urea enrichment area under
the plasma concentration-time curve over 2 hours (AUC0-2) following
each 15NH4Cl diagnostic tracer administration
o to subjects with neonatal-onset UCD (Weeks 0, 12, 24 and 36).
o to subjects with infantile-onset UCD (Weeks 0, 12, 24 and 36).
o to subjects without UCD (Weeks 0 and 12).
•The inter-subject inter-occasion variability of the [15N] urea
enrichment area under the plasma concentration-time curve over 2
hours (AUC0-2) following
o up to 4 15NH4Cl diagnostic tracer administrations over a 36-week
period to subjects with neonatal-onset UCD.
o up to 4 15NH4Cl diagnostic tracer administrations over a 36-week
period to subjects with infantile-onset UCD.
o up to 2 15NH4Cl diagnostic tracer administrations over a 12-week
period to subjects without UCD.
The inter-subject variance of the area under the blood concentrationtime curve over 2 hours (AUC0-2) for ammonia, citrulline and glutamine
following
o up to 4 15NH4Cl diagnostic tracer administrations over a 36-week
period to subjects with UCD.
o up to 2 15NH4Cl diagnostic tracer administrations over a 12-week
period to subjects without UCD
Safety Endpoints:
•Adverse events (AEs); physical, neurological and child development
examination findings; vital signs; clinical laboratory tests; biochemical
parameters; plasma amino acid levels; frequency and severity of
hyperammonaemia events and crises; and compliance to protein intake
and concomitant medication.

Secondary ID(s)

HLSC-UCD-01

2021-000824-36-ES

Ethics review

Status: Approved
Approval date: 04/04/2022
Contact: