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

Ornithine Transcarbamylase Deficiency Clinical Trial

Official title:

A Phase 1b Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Clinically Stable Patients With Ornithine Transcarbamylase Deficiency

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04442347
• Other study ID #: ARCT-810-02
• Status: Active, not recruiting
• Phase: Phase 1
• 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
• 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

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