Study for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810

Ornithine Transcarbamylase Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05526066
• Other study ID #: ARCT-810-03
• Status: Recruiting
• Phase: Phase 2
• Start date: July 6, 2022
• Est. completion date: June 2024

Study information

• Verified date: April 2023
• Source: Arcturus Therapeutics, Inc.
• Contact: David Geller, MD
• Phone: 224-727-7636
• Email: davidg[@]arcturusrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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 confirmed with genetic testing

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 OTC gene therapy, hepatocyte or stem cell transplantation

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

Related Conditions & MeSH terms

• Ornithine Transcarbamylase Deficiency
• OTC Deficiency

Intervention

Biological:
• ARCT-810
ARCT-810 is messenger RNA (mRNA) coding for Ornithine Transcarbamylase (OTC) formulated in a lipid nanoparticle (LNP) under development.

Other:
• Placebo
Normal Saline

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint Luc	Bruxelles
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Sant Joan de Déu	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario	Santiago de Compostela
Sweden	Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus	Stockholm
United Kingdom	University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham	Birmingham	UK
United Kingdom	Great Ormond Street Hospital for Children NHS Foundation Trust	London	UK
United Kingdom	University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery	London

Sponsors (1)

Lead Sponsor	Collaborator
Arcturus Therapeutics, Inc.

Countries where clinical trial is conducted

Belgium,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity and dose-relationship of adverse events (AEs)	Safety and tolerability of ARCT-810 assessed by determining the number of AEs by dose	Week 23
Secondary	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
Secondary	Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810	The maximum observed plasma concentration (Cmax)	Up to 17 Weeks
Secondary	Time at which Cmax occurred after first and last doses of ARCT-810	The time at which Cmax occurred (Tmax)	Up to 17 Weeks
Secondary	AUC0-inf after first and last doses of ARCT-810	Plasma AUC from time zero extrapolated to infinity	Up to 17 Weeks
Secondary	AUCExtrap after first and last doses of ARCT-810	The relative portion of AUC0-inf extrapolated beyond AUC0-t	Up to 17 Weeks
Secondary	T1/2 after first and last doses of ARCT-810	Terminal half-life	Up to 17 Weeks
Secondary	MRT0-inf after first and last doses of ARCT-810	The mean residence time extrapolated to infinity	Up to 17 Weeks
Secondary	CL after first and last doses of ARCT-810	Total body clearance, calculated as dose divided by AUC0-inf	Up to 17 Weeks
Secondary	Vss after first and last doses of ARCT-810	Volume of distribution	Up to 17 Weeks
Secondary	Urea Cycle Function	Change from baseline in urea cycle function as measured by 13C-urea assay	Week 12
Secondary	Plasma Ammonia	Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile	Week 11