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Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04442347
Recruitment Status : Recruiting
First Posted : June 22, 2020
Last Update Posted : July 22, 2021
Information provided by (Responsible Party):
Arcturus Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Ornithine Transcarbamylase Deficiency Biological: ARCT-810 Other: Placebo Phase 1

Detailed Description:

This is a single ascending dose study of ARCT-810 in which approximately 12 (up to a maximum of 20) subjects are planned to be enrolled. The length of each study participant is approximately 8 weeks from screening to last study visit. The study comprises an up to 4-week Screening and a 4-week Diet Run-in period to run 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 different study groups (also called cohorts), to test different doses of ARCT-810. There will be 4 participants in each group. Within each cohort, subjects will be randomized 3 :1 to receive ARCT-810 or placebo as an IV infusion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double Blinded, Placebo Controlled
Primary Purpose: Treatment
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
Actual Study Start Date : November 3, 2020
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2021

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 Ornithine Transcarbamylase (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.

Primary Outcome Measures :
  1. Incidence, severity and dose-relationship of adverse events (AEs) [ Time Frame: 4 weeks ]
    Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose

Secondary Outcome Measures :
  1. Change in area under the curve after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point

  2. Maximum observed plasma concentration (Cmax) after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    The maximum observed plasma concentration (Cmax)

  3. Time at which Cmax occurred after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    The time at which Cmax occurred (Tmax)

  4. AUC0-inf after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    AUC from time zero extrapolated to infinity

  5. AUCExtrap after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    The relative portion of AUC0-inf extrapolated beyond AUC0-t

  6. T1/2 after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    Terminal half-life

  7. MRT0-inf after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    The mean residence time extrapolated to infinity

  8. CL after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    Total body clearance, calculated as dose divided by AUC0-inf

  9. Vss after single dose of ARCT-810 [ Time Frame: Up to 4 weeks ]
    Volume of distribution

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males and females ≥18 years of age with documented diagnosis of late onset OTC deficiency confirmed with genetic testing.
  • Subject's Ornithine Transcarbamylase deficiency (OTCD) is stable as evidenced by a) no clinical symptoms of hyperammonemia and b) 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 for ≥ 28 days prior to signing informed consent and must remain on the same regimen throughout the screening period
  • Must have maintained a stable protein restricted diet +/- amino acid supplementation for at least 28 days prior to signing informed consent and continue to maintain a stable diet for the duration of the study
  • No clinically significant abnormal findings on medical history, clinical laboratory test results (other than ammonia) vital sign measurements, 12-lead ECG results, or physical examination
  • Males must be surgically sterile or willing to use adequate contraception; females must be post-menopausal, surgically sterile or willing to use adequate contraception

Exclusion Criteria:

  • History of clinically significant disease(s) (other than OTCD)
  • Abnormal hepatic enzymes, significant renal impairment, clinically significant anemia or uncontrolled diabetes
  • Blood Pressure greater than 160/100 mm Hg
  • Malignancy within 5 years prior to study
  • Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational drug, whichever is longer
  • Gene therapy within 1 year prior to screening
  • Prior organ transplant
  • Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04442347

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Contact: Steve Hughes, MD 858-900-2660
Contact: Arcturus Clinical Trials 858-900-2660

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United States, Minnesota
M Health Fairview Masonic Children's Hospital Recruiting
Minneapolis, Minnesota, United States, 55454
United States, New York
The Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
United States, Pennsylvania
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
University of Texas Southwestern Medical Center at Dallas Recruiting
Dallas, Texas, United States, 75390
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Arcturus Therapeutics, Inc.
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Responsible Party: Arcturus Therapeutics, Inc. Identifier: NCT04442347    
Other Study ID Numbers: ARCT- 810-02
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: July 22, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ornithine Carbamoyltransferase Deficiency Disease
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
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases