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Phase 1b Study to Assess 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04442347
Recruitment Status : Active, not recruiting
First Posted : June 22, 2020
Last Update Posted : April 7, 2023
Sponsor:
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 (OTCD).

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) 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.

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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 : August 2023
Estimated Study Completion Date : August 2023


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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 ClinicalTrials.gov identifier (NCT number): NCT04442347


Locations
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United States, Florida
University of Florida
Gainesville, Florida, United States, 32608
United States, Minnesota
M Health Fairview Masonic Children's Hospital
Minneapolis, Minnesota, United States, 55454
United States, New York
The Mount Sinai Hospital
New York, New York, United States, 10029
United States, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Baylor University
Waco, Texas, United States, 76706
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
Children's Wisconsin - Milwaukee Hospital
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Arcturus Therapeutics, Inc.
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Responsible Party: Arcturus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04442347    
Other Study ID Numbers: ARCT-810-02
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: April 7, 2023
Last Verified: April 2023

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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