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
Conditions
Sponsors
Unicyte AG
Eligibility
Sex/Gender
All
Inclusion 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 subject. Are the trial subjects under 18? yes Number of subjects for this age range: 30 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the intra-subject inter-occasion variability of ureagenesis in neonates with a confirmed diagnosis of UCD over a period of up to 36 weeks using a 15NH4Cl diagnostic tracer.;Secondary Objective: Key Secondary Objectives: • 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. ;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.;Timepoint(s) of evaluation of this end point: Over a 36-week period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key 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 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 neo | — |
Countries
Austria, Belgium, France, Germany, Israel, Italy, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom
Contacts
Public ContactHead Project Management&Operations
Unicyte AG
Outcome results
None listed