Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency

NCT ID: NCT04442347

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-03
• Study Completion Date: 2024-04-30

Brief Summary

Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia scavengers) with ornithine transcarbamylase deficiency (OTCD).

Detailed Description

This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum of 20) clinically stable patients with ornithine transcarbamylase deficiency (OTCD) are planned to be enrolled.

Each study subject's participation length is approximately 8 weeks, from screening through last study visit. The study comprises an up to 4-week screening period, and a 4-week diet run-in period, to occur concurrently, followed by a 1-day dosing period and a 28-day post-treatment period.

Study participants will be allocated to one of the three single-dose treatment groups (also referred to as cohorts), to test different doses of ARCT-810. Four subjects will be enrolled in each group. Within each cohort, subjects will be randomized 3:1 to receive ARCT-810 or placebo as an IV infusion.

Conditions

Ornithine Transcarbamylase Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ARCT-810

Ascending single doses of ARCT-810 administered intravenously

Group Type: EXPERIMENTAL

ARCT-810

Intervention Type: BIOLOGICAL

ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) mRNA formulated in a lipid nanoparticle (LNP) under development.

Placebo

Single doses of 0.9% Saline administered intravenously

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo for this study is 0.9% sterile saline.

Interventions

ARCT-810

ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) mRNA formulated in a lipid nanoparticle (LNP) under development.

Intervention Type: BIOLOGICAL

Placebo

The placebo for this study is 0.9% sterile saline.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Adequate cognitive ability to consent and recall symptoms over a 1-week time period

2. Males and females ≥18 years of age with documented diagnosis of ornithine transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to consent to OTC gene sequencing and deletion/duplication testing

3. Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by

1. no clinical symptoms of hyperammonemia AND

2. an ammonia level <100 µmol/L (170 µg/dL) at the screening evaluation

Subjects must remain free from symptoms of hyperammonemia throughout the screening period.

4. If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in dose or frequency) for ≥ 28 days prior to providing informed consent and throughout the screening period

5. Must have maintained a stable protein-restricted diet (+/- amino acid supplementation) for at least 28 days prior to providing informed consent and continue to maintain a stable diet for the duration of the study

6. Good general health other than OTCD, in the opinion of the Investigator

7. Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before study visits

8. Willingness to comply with procedures and visits

9. Willingness to follow contraception guidelines

Exclusion Criteria

1. History of clinically significant disease(s), in the opinion of the Investigator

2. Clinically significant screening laboratory values

3. Uncontrolled diabetes

4. Clinically significant anemia

5. Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing

6. Unwillingness to comply with study requirements

7. History of positive HIV, hepatitis C, or chronic hepatitis B

8. Uncontrolled hypertension

9. Malignancy within 5 years prior to study

10. Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug

11. Treatment with any oligonucleotide or mRNA within 6 months of screening, with exceptions for some vaccinations and investigational treatments

12. History of gene therapy, hepatocyte or mesenchymal stem cell transplantation

13. Prior organ transplant

14. History of severe allergic reaction to a liposomal product

15. Recent history of, or current, drug or alcohol abuse

16. Dependence on inhaled (smoked or vaped) or oral cannabis products

17. Systemic corticosteroids within 6 weeks prior to screening

18. Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60 days of screening

19. Other conditions, in the opinion of the Investigator, that would make the subject unsuitable for participation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arcturus Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Gainesville, Florida, United States

M Health Fairview Masonic Children's Hospital

Minneapolis, Minnesota, United States

The Mount Sinai Hospital

New York, New York, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Baylor University

Waco, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Children's Wisconsin - Milwaukee Hospital

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

ARCT-810-02

Identifier Type: -

Identifier Source: org_study_id