Detailed Description
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.
Eligibility Criteria
Age Range: 12 years to No maximum
Inclusion Criteria:
1. Willingness and ability to comply with all the protocol requirements, complete all study visits and sign informed consent.
2. Males and Females aged ≥12 years, at Screening.
3. Documented clinical diagnosis of OTC deficiency.
4. History of symptomatic hyperammonemia or elevated plasma ammonia or glutamine with clinical stability for at least 1 month prior to Screening.
5. Medically managed for OTC deficiency and receiving a stable protein-restricted diet, dietary supplements, and/or ammonia scavenger regimen (if applicable) for at least 28 days.
6. Good general health with no clinically significant abnormal findings that would interfere with study procedures (including plasma ammonia within participant's historical range).
7. Must be willing to adhere to contraception guidelines.
Exclusion Criteria:
1. Uncontrolled hypertension.
2. Symptoms of infection for at least 7 days prior to dosing.
3. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
4. History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 2 years.
5. History of any organ transplant.
6. History of severe allergic reaction to a liposomal or PEG-containing product.
7. History of congenital or acquired cardiac disorders.
8. Abuse of medications, illicit drugs or alcohol.
9. Blood donation of 50 to 499 mL within 30 days of screening or of \>499 mL within 60 days of screening.
10. Clinically significant laboratory abnormalities on screening labs including INR \>1.5, eGFR\< 60 mL/min/1.73m2 or positive test results for HIV, HBV, or HCV.
11. Inadequately controlled diabetes.
12. Clinically significant anemia.
13. Changes in maintenance therapies for OTC deficiency with 28 days prior to dosing.
14. Medical history requiring continuous or intermittent systemic corticosteroid administration.
15. Receipt of inhibitors of urea synthesis or drugs that significantly affect renal clearance.
16. Recent treatment with another investigational drug, biological agent, or device.
17. Treatment with any oligonucleotide (siRNA or mRNA) within 6 months prior to screening. COVID-19 vaccines are not exclusionary.
18. Involved in study conduct or an immediate family member of an individual involved in the study.
19. Participated in another dosing cohort of the study.
20. Any other conditions, in the opinion of the investigator, that would interfere with participation.