Safety, Tolerability and Pharmacokinetics of ARCT-810 in Healthy Adult Subjects

A Phase 1 Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Healthy Adult Subjects

Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in healthy adult subjects.

Study Overview

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

Detailed Description

This is a single ascending dose study of ARCT-810 in which approximately 30 subjects are planned to be enrolled. The length of each study participant is approximately 8 weeks from screening to last study visit.

Study participants will be allocated to one of the five different study groups (also called cohorts), to test different doses of ARCT-810. There will be 6 participants in each group. Within each cohort, subjects will be randomized 2:1 to receive ARCT-810 or placebo as an IV infusion.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies (ACS) Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy males or females aged 18 to 65 at the time of informed consent.
2. Body weight ≤ 100Kg and body mass index <35 kg/m2
3. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) and alcohol for at least 72 hours prior to study visits and willing to refrain from taking protein supplements for the duration of the study.
4. Willing and able to comply with protocol-defined procedures and complete all study visits
5. Males must be surgically sterile or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days after the last dose of Study Drug. Females: must be non-pregnant and non-lactating and either: i. surgically sterile or ii. post-menopausal

Exclusion Criteria:

1. Clinically significant abnormalities in medical history

2. Screening laboratory results as follows:

   • ALT, AST, GGT, total bilirubin or alkaline phosphatase, > ULN.
   • Random blood glucose and/or HbA1c > ULN
   • Hemoglobin < LLN
   • Platelet count < 100x109/L
   • Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated by Modification to Diet in Renal Disease [MDRD] study equation.
   • Urine protein:creatinine ratio (UPCR) > 50 mg/mmol
3. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed within 7 days prior to Study Day 1
4. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
5. Uncontrolled hypertension (BP > 160/100 mm Hg)
6. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational drug, whichever is longer
7. Recent (within 1 year) history of, or current drug or alcohol abuse
8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARCT-810; Ascending single doses of ARCT-810 administered intravenously	Biological: ARCT-810; ARCT-810 is an investigational medicinal product comprising OTC mRNA formulated in a lipid nanoparticle (LNP) under development.
Placebo Comparator: Placebo; Single doses of 0.9% Saline administered intravenously	Other: Placebo; The placebo for this study is 0.9% sterile saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and dose-relationship of AEs	Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with changes in plasma pharmacokinetic parameters after single dose of ARCT-810	The plasma pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose	Up to 15 days
Number of participants with changes in urine pharmacokinetic parameters after single dose of ARCT-810	The urine pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose	Up to 24 hours

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.
• Investigators: Principal Investigator: Christian Schwabe, MD, Auckland Clinical Studies (ACS) Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): December 9, 2020

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease
• Other Study ID Numbers: ARCT- 810-01

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.: Yes