Overview
The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.
Description
This study is a Phase 2, randomized, placebo-controlled study of ARCT-810 in people living with OTC deficiency 12 years of age and older. After a 4-6-week screening and diet stabilization period, participants will be randomized 3:1 to receive ARCT-810 or placebo. Following the first dose and safety evaluation, participants will receive up to an additional 5 doses of ARCT-810 or placebo, each separated by 14 days. The treatment period is followed by a 12-week observation period.
Eligibility
Key Inclusion Criteria:
- Adequate cognitive ability to understand study requirements and give informed consent
- Males and females aged 12 to 65 years inclusive, at Screening
- Documented diagnosis of OTC deficiency confirmed with genetic testing
- Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
- Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
- BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents ≥12 to 17 years
- Must be willing to adhere to contraception guidelines
Key Exclusion Criteria:
- History of OTC gene therapy, hepatocyte or stem cell transplantation
- History of other medical conditions that may make the participant unsuitable for inclusion or could interfere with study participation (e.g., uncontrolled hypertension or diabetes, malignancy, HIV, hepatitis B or C)
- History of severe allergic reaction to liposomal or PEG-containing products
- Abuse of illicit drugs, medications or alcohol
- Clinically significant laboratory abnormalities on screening labs