Safety, Tolerability and Pharmacokinetics of ARCT-810 in Healthy Adult Subjects

Study Overview
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Brief Summary
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Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in healthy adult subjects.

Detailed Description
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This is a single ascending dose study of ARCT-810 in which approximately 30 subjects are planned to be enrolled. The length of each study participant is approximately 8 weeks from screening to last study visit. Study participants will be allocated to one of the five different study groups (also called cohorts), to test different doses of ARCT-810. There will be 6 participants in each group. Within each cohort, subjects will be randomized 2:1 to receive ARCT-810 or placebo as an IV infusion.

Official Title
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A Phase 1 Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Healthy Adult Subjects

Conditions
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Ornithine Transcarbamylase Deficiency

Intervention / Treatment
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* Biological: ARCT-810
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females aged 18 to 65 at the time of informed consent. Body weight ≤ 100Kg and body mass index <35 kg/m2 Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) and alcohol for at least 72 hours prior to study visits and willing to refrain from taking protein supplements for the duration of the study. Willing and able to comply with protocol-defined procedures and complete all study visits Males must be surgically sterile or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days after the last dose of Study Drug. Females: must be non-pregnant and non-lactating and either: i. surgically sterile or ii. post-menopausal Exclusion Criteria: Clinically significant abnormalities in medical history Screening laboratory results as follows: ALT, AST, GGT, total bilirubin or alkaline phosphatase, > ULN. Random blood glucose and/or HbA1c > ULN Hemoglobin < LLN Platelet count < 100x109/L Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated by Modification to Diet in Renal Disease [MDRD] study equation. Urine protein:creatinine ratio (UPCR) > 50 mg/mmol Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed within 7 days prior to Study Day 1 Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B Uncontrolled hypertension (BP > 160/100 mm Hg) Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational drug, whichever is longer Recent (within 1 year) history of, or current drug or alcohol abuse Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARCT-810<br>Ascending single doses of ARCT-810 administered intravenously | Biological: ARCT-810<br>* ARCT-810 is an investigational medicinal product comprising OTC mRNA formulated in a lipid nanoparticle (LNP) under development.<br>|
| Placebo Comparator: Placebo<br>Single doses of 0.9% Saline administered intravenously | Other: Placebo<br>* The placebo for this study is 0.9% sterile saline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity and dose-relationship of AEs | Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with changes in plasma pharmacokinetic parameters after single dose of ARCT-810 | The plasma pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose | Up to 15 days | 
| Number of participants with changes in urine pharmacokinetic parameters after single dose of ARCT-810 | The urine pharmacokinetics (concentration-time results) of ARCT-810 will be assessed following single dose | Up to 24 hours |