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

Phase 2

Active, not recruiting

• Conditions: OTCD; Ornithine Transcarbamylase Deficiency; OTC Deficiency
• Interventions: Biological: ARCT-810; Other: Placebo

• Registration Number: NCT05526066
• Lead Sponsor: Arcturus Therapeutics, Inc.

Brief Summary

The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered 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 Timeline

• Study Start: 2022-07-06
• Study First Submitted: 2022-08-08
• Study First Submitted QC: 2022-08-30
• Study First Posted: 2022-09-02
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2024-12
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 24

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ARCT-810	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.
Placebo, Normal Saline	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Incidence, severity and dose-relationship of adverse events (AEs)	Week 23	Safety and tolerability of ARCT-810 assessed by determining the number and severity of AEs by dose level

Secondary Outcome Measures

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

Trial Locations

Locations (14)

Cliniques Universitaires Saint Luc; 🇧🇪 Bruxelles, Belgium

Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France

Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hôpitaux Universitaires de Marseille - Hôpital de la Timone; 🇫🇷 Marseille, France

IRCCS Ospedale Pediatrico Bambino Gesu; 🇮🇹 Rome, Italy

Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario; 🇪🇸 Santiago de Compostela, Spain

Hospital Sant Joan de Déu; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus; 🇸🇪 Stockholm, Sweden

Great Ormond Street Hospital for Children NHS Foundation Trust; 🇬🇧 London, UK, United Kingdom

University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham; 🇬🇧 Birmingham, UK, United Kingdom

Salford Royal NHS Foundation Trust - Salford Royal Hospital; 🇬🇧 Salford, United Kingdom

University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery; 🇬🇧 London, United Kingdom