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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04442347
Other study ID # ARCT-810-02
Secondary ID
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date November 3, 2020
Est. completion date August 2023

Study information

Verified date April 2023
Source Arcturus Therapeutics, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 12
Est. completion date August 2023
Est. primary completion date August 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 b, 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

Study Design


Related Conditions & MeSH terms

  • Ornithine Transcarbamylase Deficiency

Intervention

Biological:
ARCT-810
ARCT-810 is an investigational medicinal product comprising Ornithine Transcarbamylase (OTC) mRNA formulated in a lipid nanoparticle (LNP) under development.
Other:
Placebo
The placebo for this study is 0.9% sterile saline.

Locations

Country Name City State
United States University of Texas Southwestern Medical Center at Dallas Dallas Texas
United States University of Florida Gainesville Florida
United States Children's Wisconsin - Milwaukee Hospital Milwaukee Wisconsin
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 Utah Salt Lake City Utah
United States Baylor University Waco Texas

Sponsors (1)

Lead Sponsor Collaborator
Arcturus Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

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 incidence, severity and dose-relationship of AEs by dose 4 weeks
Secondary Change in area under the curve after single dose of ARCT-810 Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point Up to 4 weeks
Secondary Maximum observed plasma concentration (Cmax) after single dose of ARCT-810 The maximum observed plasma concentration (Cmax) Up to 4 weeks
Secondary Time at which Cmax occurred after single dose of ARCT-810 The time at which Cmax occurred (Tmax) Up to 4 weeks
Secondary AUC0-inf after single dose of ARCT-810 AUC from time zero extrapolated to infinity Up to 4 weeks
Secondary AUCExtrap after single dose of ARCT-810 The relative portion of AUC0-inf extrapolated beyond AUC0-t Up to 4 weeks
Secondary T1/2 after single dose of ARCT-810 Terminal half-life Up to 4 weeks
Secondary MRT0-inf after single dose of ARCT-810 The mean residence time extrapolated to infinity Up to 4 weeks
Secondary CL after single dose of ARCT-810 Total body clearance, calculated as dose divided by AUC0-inf Up to 4 weeks
Secondary Vss after single dose of ARCT-810 Volume of distribution Up to 4 weeks
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Recruiting NCT06255782 - An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency (OTC-HOPE) Phase 1/Phase 2