Study for Adolescents and Adults With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810

Phase 2, Randomized, Double-Blind, Placebo-Controlled, Nested Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARCT-810 in Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency

The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.

Study Overview

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

Detailed 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 an at least 4 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
• France
  • Marseille, France, 13005
    • Hôpitaux Universitaires de Marseille - Hôpital de la Timone
  • Paris, France
    • Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
• Italy
  • Padua, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Rome, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
• Spain
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Barcelona, Spain
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
• Sweden
  • Stockholm, Sweden, SE- 171 64
    • Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus
• United Kingdom
  • London, United Kingdom
    • University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust - Salford Royal Hospital
  • UK
    • Birmingham, UK, United Kingdom, B15 2PR
      • University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
    • London, UK, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Adequate cognitive ability to understand study requirements and give informed consent
2. Males and females aged 12 to 65 years inclusive, at Screening
3. Documented diagnosis of OTC deficiency
4. Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
5. Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
6. BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents ≥12 to 17 years
7. Must be willing to adhere to contraception guidelines

Key Exclusion Criteria:

1. History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 3 years
2. 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)
3. History of severe allergic reaction to liposomal or PEG-containing products
4. Abuse of illicit drugs, medications or alcohol
5. Clinically significant laboratory abnormalities on screening labs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARCT-810; Participants receive an initial intravenous (IV) infusion ARCT-810. If considered safe and well tolerated, participants will receive up to 5 additional IV infusions of ARCT-810 administered at 14-day intervals.	Biological: ARCT-810; ARCT-810 is messenger RNA (mRNA) coding for Ornithine Transcarbamylase (OTC) formulated in a lipid nanoparticle (LNP).
Placebo Comparator: Placebo, Normal Saline; Participants receive an initial IV infusion of placebo. If considered safe and well tolerated, participants receive up to 5 additional IV infusions of placebo administered at 14-day intervals.	Other: Placebo; Normal Saline

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 determining the number and severity of AEs by dose level	Week 23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration area under the curve after first and last doses of ARCT-810	Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point	Up to 17 Weeks
Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810	The maximum observed plasma concentration (Cmax)	Up to 17 Weeks
Time at which Cmax occurred after first and last doses of ARCT-810	The time at which Cmax occurred (Tmax)	Up to 17 Weeks
AUC0-inf after first and last doses of ARCT-810	Plasma AUC from time zero extrapolated to infinity	Up to 17 Weeks
AUCExtrap after first and last doses of ARCT-810	The relative portion of AUC0-inf extrapolated beyond AUC0-t	Up to 17 Weeks
T1/2 after first and last doses of ARCT-810	Terminal half-life	Up to 17 Weeks
MRT0-inf after first and last doses of ARCT-810	The mean residence time extrapolated to infinity	Up to 17 Weeks
CL after first and last doses of ARCT-810	Total body clearance, calculated as dose divided by AUC0-inf	Up to 17 Weeks
Vss after first and last doses of ARCT-810	Volume of distribution	Up to 17 Weeks
Urea Cycle Function	Change from baseline in urea cycle function as measured by 13C-urea assay	Week 12
Plasma Ammonia	Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile	Week 11

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: mRNA; OTC; OTC Deficiency; OTCD; Ornithine; Transcarbamylase; Ornithine Transcarbamylase Deficiency
• 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Ornithine Carbamoyltransferase Deficiency Disease
• Other Study ID Numbers: ARCT-810-03

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
• product manufactured in and exported from the U.S.: No