Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults With Hereditary Angioedema (HAE)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 37
- 试验地点
- 9
- 主要终点
- Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)
研究概览
简要总结
This study will be conducted to evaluate the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Hereditary Angioedema (HAE).
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
- Double (Participant, Investigator)
盲法说明
Phase 1 is an open label non-randomized study Phase 2 is a randomized, double-blind, placebo-controlled study
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
- •Age >18 years
- •Diagnosis of HAE Types I or II
- •Ability to provide evidence of HAE attacks to meet the screening requirement
- •Subjects must have access to, and the ability to use, ≥ 1 acute medication(s) to treat angioedema attacks.
- •Adequate chemistry and hematology measures at screening
- •Subjects must agree not to participate in another interventional study for the duration of this trial.
- •Subjects must be capable of providing signed informed consent
排除标准
- •Concurrent diagnosis of any other type of recurrent angioedema
- •Subjects who have known negative reaction or hypersensitivity to any lipid nanoparticles (LNP) component.
- •Any condition that, in the Investigator's opinion, could adversely affect the safety of the subject.
- •Unwilling to comply with study procedures.
研究组 & 干预措施
Phase 1 Study Arm
Participants assigned to 1 of 3 dose-escalation cohorts will receive a single dose of NTLA-2002 on Day 1 and will then be followed for 104 weeks. Primary observation period is 16 weeks.
干预措施: Biological NTLA-2002 (Biological)
Phase 2 Experimental Study Arm
Participants randomized to NTLA-2002 (2 dose levels), will receive a single dose of NTLA-2002 on Day 1 and will then be followed for 104 weeks. Primary observation period is 16 weeks.
干预措施: Biological NTLA-2002 (Biological)
Phase 2 Placebo Comparator Study Arm
Participants randomized to placebo will receive IV normal saline on Day 1 and will then be followed for up to 104 weeks. Primary observation period is 16 weeks.
干预措施: Normal Saline IV Administration (Other)
Placebo Crossover and Follow-On Dosing Substudy Arm
Participants assigned to this Substudy Arm (participants who previously received either 25mg or placebo only) will have the opportunity to receive a single dose of NTLA-2002 (50mg) and will then be followed for 52 weeks.
干预措施: Biological NTLA-2002 (Biological)
结局指标
主要结局
Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)
时间窗: From NTLA-2002 infusion up to week 104 post-infusion
(Phase 1 only)
Number of HAE attacks per month (Weeks 1-16)
时间窗: From study drug infusion up to week 16 post-infusion
(Phase 2 only)
次要结局
- Number of HAE attacks per month requiring acute therapy (Weeks 1-16, Weeks 5-16)(From study drug infusion up to week 16 post-infusion)
- Change from baseline in total plasma kallikrein protein level(From NTLA-2002 infusion up to week 104 post-infusion)
- Number of HAE attacks per month (Weeks 5-16)(From week 6 post-infusion up to week 16 post-infusion)
- Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA(From NTLA-2002 infusion up to week 104 post-infusion)
- Safety and tolerability of NTLA-2002 as determined by AEs(From study drug infusion up to week 104 post-infusion)