Clinical trial assessing urea formation capacity in children up to 10 years of age using 15N ammonium chloride tracer
- Conditions
- 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 (subjects without UCD will not be enrolled in Germany)Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]MedDRA version: 20.1Level: PTClassification code 10080020Term: Urea cycle disorderSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
- Registration Number
- EUCTR2021-000824-36-DE
- Lead Sponsor
- nicyte AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
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 (subjects without UCD will not be enrolled in Germany):
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 10 years, inclusive;
5.Subject has a body weight within the 5-95th percentile of the corresponding age according to the CDC Growth Charts;
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 for the duration of the trial until the final follow-up visit;
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, and assent from the pediatric subject when required by local regulations, the IRB/IEC or trial site.
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
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 without UCD (subjects without UCD will not be enrolled in Germany):
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.
7. Subject has abnormal renal function, or an estimated glomerular filtration rate (eGFR) of below 40 mL/min/1.73 m2 (aged up to 2 years) or below 60 mL/min/1.73 m2 (aged 2 to 10 years), as calculated by the pediatric Schwartz equation. This assessment may be repeated once to exclude spurious values.
8. Subject has a supine or semi-supine systolic blood pressure below 60 mm Hg, or a supine or semi-supine heart rate (HR) outside the range of 90-180 bpm (aged up to 28 days), or 110-160 bpm (aged 1 to 12 months), 100-150 bpm (aged 1 to 5 years) or 80-120 bpm (aged 5 to 10 years), confirmed on repeat testing (WHO Pocket Book of Hospital Care for Children 2013, Samuels 2010).
9. Subject has abnormal electrocardiogram (ECG) values as follows, based on the mean of the triplicate ECG values, and confirmed on repeat triplicate testing (Lambrechts and Fourie 2020):
o PR interval above 120 msec (aged up to 28 days), or 140 msec (aged 1 to 12 months), 170 msec (aged 1 to 5 years) or 190 msec (aged 5 to 10 years);
o QRS interval above 70 msec (aged up to 28 days), or 75 msec for infants (aged 1 to 12 months), 110 msec (aged 1 to 5 years) or 120 msec (aged 5 to 10 years);
o QT interval corrected for HR using Fridericia’s formula (QTcF) above 420 msec for neonates (aged up to 28 days) or 440 msec for infants (aged 1 to 10
years);
10. Subject has haemoglobin levels outside the pediatric-specific normal range of the local laboratory. The test may be repeated once to exclude spurious values.
11. Subject has any clinical or laboratory abnormality of Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE) v5, except Grade 3 elevations in ammonia, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma glutamyl transpeptidase (GGT) in a clinically stable subject. The test(s) may be repeated once to exclude spurious values.
12. Subject has any other clinically significant abnormal physical examination, vital signs, ECG or laboratory finding that, according to the judgement of the investigator, may put the subject at increased risk by participating in this study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method