Phase 2, Randomized, Double-Blind, Placebo-Controlled, Nested Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARCT-810 in Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 14
- 主要终点
- Incidence, severity and dose-relationship of adverse events (AEs)
研究概览
简要总结
The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-Blinded
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adequate cognitive ability to understand study requirements and give informed consent
- •Males and females aged 12 to 65 years inclusive, at Screening
- •Documented diagnosis of OTC deficiency
- •Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
- •Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
- •BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and >5th percentile for adolescents ≥12 to 17 years
- •Must be willing to adhere to contraception guidelines
排除标准
- •History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 3 years
- •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)
- •History of severe allergic reaction to liposomal or PEG-containing products
- •Abuse of illicit drugs, medications or alcohol
- •Clinically significant laboratory abnormalities on screening labs
研究组 & 干预措施
ARCT-810
Participants receive an initial intravenous (IV) infusion ARCT-810. If considered safe and well tolerated, participants will receive up to 5 additional IV infusions of ARCT-810 administered at 14-day intervals.
干预措施: ARCT-810 (Biological)
Placebo, Normal Saline
Participants receive an initial IV infusion of placebo. If considered safe and well tolerated, participants receive up to 5 additional IV infusions of placebo administered at 14-day intervals.
干预措施: Placebo (Other)
结局指标
主要结局
Incidence, severity and dose-relationship of adverse events (AEs)
时间窗: Week 23
Safety and tolerability of ARCT-810 assessed by determining the number and severity of AEs by dose level
次要结局
- AUC0-inf after first and last doses of ARCT-810(Up to 17 Weeks)
- T1/2 after first and last doses of ARCT-810(Up to 17 Weeks)
- MRT0-inf after first and last doses of ARCT-810(Up to 17 Weeks)
- Plasma Ammonia(Week 11)
- Time at which Cmax occurred after first and last doses of ARCT-810(Up to 17 Weeks)
- AUCExtrap after first and last doses of ARCT-810(Up to 17 Weeks)
- CL after first and last doses of ARCT-810(Up to 17 Weeks)
- Plasma concentration area under the curve after first and last doses of ARCT-810(Up to 17 Weeks)
- Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810(Up to 17 Weeks)
- Urea Cycle Function(Week 12)
- Vss after first and last doses of ARCT-810(Up to 17 Weeks)