A Study to Evaluate the Pharmacodynamics and Safety of ARCT-810 in Participants With OTCD

A Phase 2a, Open-label, Multiple Ascending Dose Study to Evaluate the Pharmacodynamics and Safety of ARCT-810 in Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency

Evaluate the safety and pharmacodynamics of multiple doses of ARCT-810 in adolescent and adult participants with OTC deficiency.

Study Overview

• Status: Recruiting
• Conditions: OTC Deficiency; Ornithine Transcarbamylase Deficiency; OTCD
• Intervention / Treatment: Biological: ARCT-810

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Recruiting
      • Uncommon Cures
      • Contact: Marshall Summar, MD; Phone Number: 541-232-7818; Email: arcturus@uncommoncures.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARCT-810; Participants will receive up to 5 IV infusions of ARCT-810 administered at 14-day intervals.	Biological: ARCT-810; ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) messenger RNA (mRNA) formulated in a lipid nanoparticle (LNP).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and dose-relationship of adverse events (AEs)	Safety and tolerability of ARCT-810 assessed by incidence, severity, and dose-relationship of AEs	Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Up to Day 85
Fasting plasma ammonia	Proportion of participants maintaining normal morning fasting plasma ammonia	Up to Day 85
Plasma Glutamine	Change from Baseline in plasma glutamine and labeled glutamine as available	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	Up to Day 57

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Genetic Diseases, X-Linked; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease
• Other Study ID Numbers: ARCT-810-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No