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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 8
- 主要终点
- Incidence, severity and dose-relationship of adverse events (AEs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double Blinded, Placebo Controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adequate cognitive ability to consent and recall symptoms over a 1-week time period
- •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
- •Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by
- •no clinical symptoms of hyperammonemia AND
- •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.
- •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
- •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
- •Good general health other than OTCD, in the opinion of the Investigator
- •Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before study visits
- •Willingness to comply with procedures and visits
- •Willingness to follow contraception guidelines
排除标准
- •History of clinically significant disease(s), in the opinion of the Investigator
- •Clinically significant screening laboratory values
- •Uncontrolled diabetes
- •Clinically significant anemia
- •Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing
- •Unwillingness to comply with study requirements
- •History of positive HIV, hepatitis C, or chronic hepatitis B
- •Uncontrolled hypertension
- •Malignancy within 5 years prior to study
- •Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug
- •Treatment with any oligonucleotide or mRNA within 6 months of screening, with exceptions for some vaccinations and investigational treatments
- •History of gene therapy, hepatocyte or mesenchymal stem cell transplantation
- •Prior organ transplant
- •History of severe allergic reaction to a liposomal product
- •Recent history of, or current, drug or alcohol abuse
- •Dependence on inhaled (smoked or vaped) or oral cannabis products
- •Systemic corticosteroids within 6 weeks prior to screening
- •Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60 days of screening
- •Other conditions, in the opinion of the Investigator, that would make the subject unsuitable for participation
研究组 & 干预措施
Placebo
Single doses of 0.9% Saline administered intravenously
干预措施: Placebo (Other)
ARCT-810
Ascending single doses of ARCT-810 administered intravenously
干预措施: ARCT-810 (Biological)
结局指标
主要结局
Incidence, severity and dose-relationship of adverse events (AEs)
时间窗: 4 weeks
Safety and tolerability of ARCT-810 assessed by determining the incidence, severity and dose-relationship of AEs by dose
次要结局
- Vss after single dose of ARCT-810(Up to 4 weeks)
- T1/2 after single dose of ARCT-810(Up to 4 weeks)
- Maximum observed plasma concentration (Cmax) after single dose of ARCT-810(Up to 4 weeks)
- AUC0-inf after single dose of ARCT-810(Up to 4 weeks)
- MRT0-inf after single dose of ARCT-810(Up to 4 weeks)
- Time at which Cmax occurred after single dose of ARCT-810(Up to 4 weeks)
- Change in area under the curve after single dose of ARCT-810(Up to 4 weeks)
- AUCExtrap after single dose of ARCT-810(Up to 4 weeks)
- CL after single dose of ARCT-810(Up to 4 weeks)