Ornithine Transcarbamylase Deficiency, OTCD, OTC Deficiency
Conditions
Keywords
OTC, OTCD, Ornithine, Transcarbamylase, mRNA, Ornithine Transcarbamylase Deficiency, OTC Deficiency
Brief summary
The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.
Detailed description
This study is a Phase 2, randomized, placebo-controlled study of ARCT-810 in people living with OTC deficiency 12 years of age and older. After an at least 4 week screening and diet stabilization period, participants will be randomized 3:1 to receive ARCT-810 or placebo. Following the first dose and safety evaluation, participants will receive up to an additional 5 doses of ARCT-810 or placebo, each separated by 14 days. The treatment period is followed by a 12-week observation period.
Interventions
BIOLOGICALARCT-810
ARCT-810 is messenger RNA (mRNA) coding for Ornithine Transcarbamylase (OTC) formulated in a lipid nanoparticle (LNP).
OTHERPlacebo
Normal Saline
Sponsors
Arcturus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-Blinded
Intervention model description
On Day 1, participants will receive a single dose of Study Drug via intravenous infusion. If the safety observations are considered acceptable, that participant will enter the multiple-dose portion of the study in which they will receive a further 5 doses of Study Drug on Days 15, 29, 43, 57 and 71.
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Adequate cognitive ability to understand study requirements and give informed consent 2. Males and females aged 12 to 65 years inclusive, at Screening 3. Documented diagnosis of OTC deficiency 4. Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year) 5. Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days. 6. BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and \>5th percentile for adolescents ≥12 to 17 years 7. Must be willing to adhere to contraception guidelines Key
Exclusion criteria
1. History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 3 years 2. History of other medical conditions that may make the participant unsuitable for inclusion or could interfere with study participation (e.g., uncontrolled hypertension or diabetes, malignancy, HIV, hepatitis B or C) 3. History of severe allergic reaction to liposomal or PEG-containing products 4. Abuse of illicit drugs, medications or alcohol 5. Clinically significant laboratory abnormalities on screening labs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity and dose-relationship of adverse events (AEs) | Week 23 | Safety and tolerability of ARCT-810 assessed by determining the number and severity of AEs by dose level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810 | Up to 17 Weeks | The maximum observed plasma concentration (Cmax) |
| Time at which Cmax occurred after first and last doses of ARCT-810 | Up to 17 Weeks | The time at which Cmax occurred (Tmax) |
| AUC0-inf after first and last doses of ARCT-810 | Up to 17 Weeks | Plasma AUC from time zero extrapolated to infinity |
| AUCExtrap after first and last doses of ARCT-810 | Up to 17 Weeks | The relative portion of AUC0-inf extrapolated beyond AUC0-t |
| T1/2 after first and last doses of ARCT-810 | Up to 17 Weeks | Terminal half-life |
| Plasma concentration area under the curve after first and last doses of ARCT-810 | Up to 17 Weeks | Area under the plasma concentration versus time curve (AUC) from time zero to the last quantifiable time point |
| CL after first and last doses of ARCT-810 | Up to 17 Weeks | Total body clearance, calculated as dose divided by AUC0-inf |
| Vss after first and last doses of ARCT-810 | Up to 17 Weeks | Volume of distribution |
| Urea Cycle Function | Week 12 | Change from baseline in urea cycle function as measured by 13C-urea assay |
| Plasma Ammonia | Week 11 | Change from baseline in urea cycle function as measured by 24-hour plasma ammonia profile |
| MRT0-inf after first and last doses of ARCT-810 | Up to 17 Weeks | The mean residence time extrapolated to infinity |
Countries
Belgium, France, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed