NCT03767270撤回1 期
A Phase 1/2 Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered MRT5201 in Subjects With Ornithine Transcarbamylase Deficiency
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- The incidence of treatment-emergent adverse events by treatment group
研究概览
简要总结
This Phase 1/2, first-in-human study will evaluate the safety and tolerability of single escalating doses of MRT5201 administered intravenously to subjects with OTC Deficiency (OTCD). This study will also evaluate the effect of a single dose of MRT5201 on metabolic markers of OTCD and ureagenesis; and determine an acceptable dosing interval of MRT5201.
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)
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
- •Have a documented diagnosis of OTCD.
- •Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L
- •Subject's OTCD is stable as evidenced by meeting the following criteria:
- •Ammonia level <175 µmol/L during the Screening Period and at Baseline (Day -1)
- •No clinical symptoms of hyperammonemia during the Screening Period and at Baseline (Day -1)
- •If using nitrogen scavenger therapy, must be on a stable regimen for ≥28 days prior to signing informed consent
- •Subject has maintained a stable protein restricted diet (which may or may not include medical foods) 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 ≥ 28 days prior to signing informed consent.
排除标准
- •Any laboratory abnormality that may put the subject at increased risk by participating in this study.
- •Have any significant concurrent or past medical condition that would represent an unacceptable risk to the subject or might jeopardize the collection of high-quality data from the study. These include but are not limited to:
- •History of liver transplant, including hepatocyte therapy/transplant
- •History of liver disease
- •Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody
- •Type I or Type II diabetes that is poorly controlled, in the opinion of the Investigator
- •Poorly controlled hypertension (defined as systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg)
- •Use of anticoagulants or platelet inhibitors, including but not limited to heparin and non-steroidal anti-inflammatory drugs (NSAIDS). Acetaminophen is permitted
- •Participation in previous clinical studies evaluating investigational OTCD therapies directed at expressing functional OTC protein (eg, OTC gene therapy studies, other mRNA replacement therapy) that has led to the presence of anti-OTC antibodies.
研究组 & 干预措施
MRT5201
Experimental
Single Ascending Low, Mid, and High doses of MRT5201
干预措施: MRT5201 (Biological)
Placebo
Placebo Comparator
Placebo comparator using 5% dextrose in water at the same administration rate as study drug.
干预措施: Placebo (Other)
结局指标
主要结局
The incidence of treatment-emergent adverse events by treatment group
时间窗: Week 24
The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) for each dosing cohort by treatment group, assessed by severity and relationship to study product.
次要结局
- Effect of a single dose of MRT5201 on ureagenesis(Up to 1 month after single dose)
- Effect of single dose of MRT5201 on metabolic markers of OTCD(6 months after single dose)
- Pharmacokinetics parameters of MRT5201(1 month after single dose)
研究者
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