Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia scavengers) with ornithine transcarbamylase deficiency (OTCD).
This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are planned to be enrolled. Each study subject's participation length is approximately 8 weeks, from screening through last study visit. The study comprises an up to 4-week screening period, and a 4-week diet run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day post-treatment period. Study participants will be allocated to one of the three single-dose treatment groups (also referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled in each group. Within each cohort, subjects will be randomized 3:1 to receive ARCT-810 or placebo as an IV infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
16
University of Florida
Gainesville, Florida, United States
M Health Fairview Masonic Children's Hospital
Minneapolis, Minnesota, United States
The Mount Sinai Hospital
New York, New York, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
Incidence, severity and dose-relationship of adverse events (AEs)
Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose
Time frame: 4 weeks
Change in area under the curve after single dose of ARCT-810
Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point
Time frame: Up to 4 weeks
Maximum observed plasma concentration (Cmax) after single dose of ARCT-810
The maximum observed plasma concentration (Cmax)
Time frame: Up to 4 weeks
Time at which Cmax occurred after single dose of ARCT-810
The time at which Cmax occurred (Tmax)
Time frame: Up to 4 weeks
AUC0-inf after single dose of ARCT-810
AUC from time zero extrapolated to infinity
Time frame: Up to 4 weeks
AUCExtrap after single dose of ARCT-810
The relative portion of AUC0-inf extrapolated beyond AUC0-t
Time frame: Up to 4 weeks
T1/2 after single dose of ARCT-810
Terminal half-life
Time frame: Up to 4 weeks
MRT0-inf after single dose of ARCT-810
The mean residence time extrapolated to infinity
Time frame: Up to 4 weeks
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University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States
Baylor University
Waco, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Children's Wisconsin - Milwaukee Hospital
Milwaukee, Wisconsin, United States
CL after single dose of ARCT-810
Total body clearance, calculated as dose divided by AUC0-inf
Time frame: Up to 4 weeks
Vss after single dose of ARCT-810
Volume of distribution
Time frame: Up to 4 weeks