Evaluate the safety and pharmacodynamics of multiple doses of ARCT-810 in adolescent and adult participants with OTC deficiency.
This a Phase 2a, open-label study of ARCT-810 in participants 12 years of age and older living with OTC deficiency. After a diet stabilization period of at least 4 weeks, all participants will be enrolled to receive ARCT-810 every two weeks, for up to five doses, at one of three dose levels. Clinic visits will occur during screening and at Days 1, 15, 29, 36, 43, 57, 60, 71, and 85. During the study, participants will remain on their current clinical management for OTC deficiency. Dose escalation or cohort expansion may occur following completion of three participants at each dose level.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) messenger RNA (mRNA) formulated in a lipid nanoparticle (LNP).
Uncommon Cures
Chevy Chase, Maryland, United States
RECRUITINGIncidence, severity and dose-relationship of adverse events (AEs)
Safety and tolerability of ARCT-810 assessed by incidence, severity, and dose-relationship of AEs
Time frame: Day 85
Stable isotope ureagenesis assay values (AUC of first isotope)
Change from Baseline in stable isotope ureagenesis assay values (AUC of first isotope) following multiple doses of ARCT-810
Time frame: Up to Day 85
Stable isotope ureagenesis assay values (AUC of second isotope)
Change from Baseline in stable isotope ureagenesis assay values (AUC of second isotope) following mulitple doses of ARCT-810
Time frame: Up to Day 85
Fasting plasma ammonia
Proportion of participants maintaining normal morning fasting plasma ammonia
Time frame: Up to Day 85
Plasma Glutamine
Change from Baseline in plasma glutamine and labeled glutamine as available
Time frame: Up to Day 85
Plasma pharmacokinetics
The noncompartmental plasma pharmacokinetics of ARCT-810 will be assessed based on the observed plasma concentration of ARCT-810 mRNA and lipid
Time frame: Up to Day 57
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