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

NCT04442347 | Completed Phase 1 FDA Drug

• 1 other identifier: ARCT-810-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

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).

Conditions

Ornithine Transcarbamylase Deficiency

Outcome Measures

Primary Outcomes (1)

• Incidence, severity and dose-relationship of adverse events (AEs)

  Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose

  4 weeks

Secondary Outcomes (9)

• Change in area under the curve after single dose of ARCT-810

  Up to 4 weeks

• Maximum observed plasma concentration (Cmax) after single dose of ARCT-810

  Up to 4 weeks

• Time at which Cmax occurred after single dose of ARCT-810

  Up to 4 weeks

• AUC0-inf after single dose of ARCT-810

  Up to 4 weeks

• AUCExtrap after single dose of ARCT-810

  Up to 4 weeks

Study Arms (2)

ARCT-810

EXPERIMENTAL

Ascending single doses of ARCT-810 administered intravenously

Biological: ARCT-810

Placebo

PLACEBO COMPARATOR

Single doses of 0.9% Saline administered intravenously

Other: Placebo

Interventions

ARCT-810 BIOLOGICAL

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

ARCT-810

Placebo OTHER

The placebo for this study is 0.9% sterile saline.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequate cognitive ability to consent and recall symptoms over a 1-week time period
• 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
• Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by
• no clinical symptoms of hyperammonemia AND
• 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.
• 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
• 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
• Good general health other than OTCD, in the opinion of the Investigator
• Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before study visits
• Willingness to comply with procedures and visits
• Willingness to follow contraception guidelines

You may not qualify if:

• History of clinically significant disease(s), in the opinion of the Investigator
• Clinically significant screening laboratory values
• Uncontrolled diabetes
• Clinically significant anemia
• Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing
• Unwillingness to comply with study requirements
• History of positive HIV, hepatitis C, or chronic hepatitis B
• Uncontrolled hypertension
• Malignancy within 5 years prior to study
• Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug
• Treatment with any oligonucleotide or mRNA within 6 months of screening, with exceptions for some vaccinations and investigational treatments
• History of gene therapy, hepatocyte or mesenchymal stem cell transplantation
• Prior organ transplant
• History of severe allergic reaction to a liposomal product
• Recent history of, or current, drug or alcohol abuse

Sponsors & Collaborators

• Arcturus Therapeutics, Inc.: lead

Study Sites (8)

University of Florida

Gainesville, Florida, 32608, United States

Location

M Health Fairview Masonic Children's Hospital

Minneapolis, Minnesota, 55454, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Baylor University

Waco, Texas, 76706, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Children's Wisconsin - Milwaukee Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease

Condition Hierarchy (Ancestors)

Urea Cycle Disorders, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double Blinded, Placebo Controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: June 22, 2020
• Study Start: November 3, 2020
• Primary Completion: August 30, 2023
• Study Completion: April 30, 2024
• Last Updated: August 2, 2024

Record last verified: 2024-07

Locations

US (8)