A Multi-dose Study of an Investigational Treatment to Evaluate Safety, Tolerability, and Ability to Improve Urea Cycle Function in Adolescents and Adults with Ornithine Transcarbamylase Deficiency

Phase 1

• Conditions: Ornithine transcarbamylase deficiency; MedDRA version: 21.1Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolismSystem Organ Class: 200000003094; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2021-001081-38-ES
• Lead Sponsor: Arcturus Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-31
• Last Update Posted: 17 January 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Must have adequate cognitive ability, in the opinion of the Investigator, to understand the investigational nature of the study and study requirements, to recall symptoms over a 1-week time period, and to give informed consent (ICF). Must be willing and able to comply with all the protocol requirements, complete all study visits and sign an ICF in accordance with institutional and regulatory guidelines.
2.Males and females aged 12 to 65 years inclusive, at Screening.
3.Documented diagnosis of late onset OTC deficiency confirmed with genetic testing. In participants not previously genetically confirmed, testing should include OTC gene sequencing and deletion/duplication testing.
4.No hospitalizations for metabolic decompensation within 1 year prior to the first dose of Study Drug and no clinical symptoms of hyperammonemia within 1 month prior to signing ICF.
5.If using nitrogen ammonia scavenger therapy, must be on a stable regimen for = 28 days prior to signing ICF.
6.Participant has, maintained a stable protein restricted diet and/or amino acid supplementation with no changes in calorie or protein goals and no changes in medical food and/or amino acid supplementation for at least 28 days prior to signing ICF and participant is willing to remain on the same diet for the full duration of the study. Participants may have their diet adjusted for optimization by the study dietician at the Study Center during the screening period
7.Good general health, aside from OTC deficiency and its complications, as determined by no clinically significant abnormal findings on medical history, clinical laboratory test results (other than ammonia concentrations and other biomarkers), vital sign measurements, 12-lead ECG results, or physical examination at Screening that, in the opinion of the Investigator or Sponsor Medical monitor, would interfere with Study Drug administration, jeopardize the safety of the participant, or impact the validity of the study results.
8.BMI = 18.0 – 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents =12 to 17 years old.
9.Participants must refrain from strenuous exercise/activity and consuming alcohol for at least 72 hours prior to study visits.
10.Males are eligible to participate if they agree to the following requirements during the intervention period and for at least 60 days after the last dose of study drug, which corresponds to the time needed to minimize any potential reproductive safety risk of the study drug:
a.Refrain from donating sperm, AND
b.Must agree to use a male condom when engaging in sexual relations with a female of child-bearing potential (WOCBP, defined below). In addition, a highly effective method of contraception may be considered in WOCBP partners of male participants
Male participants who are surgically sterile are exempt from using contraception.

11.Females are eligible to participate if they are not currently pregnant or breastfeeding nor planning to become pregnant or breastfeed during the study; and at least one of the following conditions applies:
a.Is not a woman of child-bearing potential (defined below)
b.Is a WOCBP and using highly effective contraceptive methods during the study intervention period and for at least 60 days after the last dose of Study Drug. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study drug.
A woman is considered fertile following menarche and until becoming pos

Exclusion Criteria

1.Uncontrolled hypertension (Systolic BP > 160 and/or diastolic BP >100 mm Hg)
2.Any participant who develops symptoms of infection, , must be asymptomatic for at least 7 days prior to dosing on Day 1. Any participant who requires systemic antimicrobial treatment must have both discontinued antimicrobial therapy for at least 7 days and be symptom free for at least 7 days prior to dosing. The screening period may be extended, , for up to 7 days without need to repeat screening evaluations. In this instance the diet run-in period should also be extended. Participants who are not free of symptoms and/or antimicrobials for at least 7 days prior to Day 1 despite the aforementioned extension of the screening period may be rescreened once medication is complete, and their clinical condition is stable for at least 7 days.
3.Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Participants with a history of other malignancies that have been treated and which have no recurrence within 5 years may also be eligible if approved by the Sponsor medical monitor
4.History of any OTC gene therapy or hepatocyte transplantation.
5.History of any organ transplant or stem cell transplant.
6.History of severe allergic reaction to a liposomal or PEG containing product.
7.Abuse of medications, illicit drugs or alcohol within 1 year prior to screening,
8.Use of cannabis products within 28 days prior to screening..
9.Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening
10.Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that, in the opinion of the Investigator or Sponsor Medical Monitor (or designee) would render a participant unsuitable for inclusion:
•ALT or AST > 2x ULN
•Total bilirubin > 1.5 mg/dL, unless due to documented Gilbert's syndrome in which case total bilirubin must be <3 mg/dL
•Platelet count < 100x10^9/L
•Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated by Modification to Diet in Renal Disease [MDRD] study equation.
•Abnormal thyroid function tests unless approved by the Sponsor Medical Monitor (or designee)
•Presence of human immunodeficiency virus antibody, hepatitis C virus antibody, or hepatitis B surface antigen
11.Diabetes that is not, , adequately controlled with diet +/- antidiabetic medication.
12.Clinically significant anemia
13.Changes in maintenance therapies within 28 days prior to Day 1. Participants who require a change in maintenance therapy may be rescreened once they have been on a stable regimen for = 28 days.
14.Treatment with oral or systemic corticosteroids within 28 days prior to Day 1 and prohibited during the study unless required to manage an IRR.
15.Treatment with acetaminophen within 28 days prior to Day 1 and prohibited during the trial unless required as part of the premedication regimen or to manage IRR if ibuprofen is contraindicated.
16.Treatment with another investigational drug, biological agent, or device within 30-days of screening, or 5 half-lives of investigational drug, whichever is longer.
17.Treatment with any oligonucleotide (including siRNA) or mRNA therapy within 6 months prior to Screening. Participants who have previously received only a single dose of an oligonucleotide or mRNA as part of a clinical study may be included if a duration =3 mo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified