A Phase 1/2 Multicenter, First-in-human, Ascending Dose Trial Evaluating the Safety, Tolerability, and Efficacy of a Lipid Nanoparticle Formulation of CRISPR-Guide RNA-Cas9 Nuclease (CTX340) for In Vivo Editing of the Angiotensinogen (AGT) Gene in Participants With Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Phase 1: Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
A Study of CTX340 in Participants with Uncontrolled Hypertension.
详细描述
This is a dose ascending study of CTX340 in participants with hypertension. Subjects will receive CTX340 or placebo via intravenous (IV) infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Phase 1 is Open-Label, while Phase 2 is Double-Blind (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: ≥18 and ≤75 years.
- •Body mass index ≤40 kg/m
- •24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP) measurement of ≥130 mm Hg but ≤160 mm Hg despite treatment
- •Be on treatment with ≥4 antihypertensive therapies at effective doses, of which ≥1 must be a diuretic.
- •Participants who at any point had childbearing potential must currently be postmenopausal
- •All participants capable of producing sperm must agree to the use of an acceptable method of effective contraception and their partners with childbearing potential should also agree to use an effective method of contraception.
排除标准
- •Serum aldosterone and direct renin concentration (or plasma renin activity [PRA]) suggestive of primary aldosteronism
- •Mean diastolic blood pressure (DBP) ≤65 mm Hg on screening ABPM.
- •Participants with vascular cause of hypertension which may be amendable to revascularization
- •Participants with treatable/reversible causes of uncontrolled hypertension
- •History of renal artery denervation within past 12 months.
- •Orthostatic hypotension
- •Complete blood count (CBC) outside the specified ranges per protocol.
- •Evidence of liver disease
- •History of a significant coagulation disorder.
- •Uncontrolled or untreated thyroid disease
研究组 & 干预措施
Phase 1: CTX340
Phase 1 is An Open-Label, Ascending Dose Design.
干预措施: CTX340 (Drug)
Phase 2: Placebo
Phase 2: Placebo.
干预措施: Placebo (Drug)
Phase 2: Recommended Phase 2 Dose CTX340
Phase 2: Recommended Phase 2 Dose CTX340.
干预措施: CTX340 (Drug)
结局指标
主要结局
Phase 1: Incidence of dose-limiting toxicities (DLTs)
时间窗: Up to 12 months
To evaluate the safety and tolerability of a single ascending dose of CTX340 in participants with hypertension to determine the recommended Phase 2 dose (RP2D).
Phase 2: Percentage change in circulating angiotensinogen (AGT) concentration from baseline
时间窗: Through 6 months of follow-up.
To evaluate the pharmacodynamics (PD) effect of CTX340 at the recommended Phase 2 dose (RP2D)
次要结局
- To assess the safety of CTX340(From CTX340 infusion up to 12 months)
- To assess the effect of CTX340 on systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM)(From CTX340 infusion up to 12 months)
- To assess the pharmacodynamics (PD) effect of CTX340(Over 12 months, compared to baseline)
- To characterize the pharmacokinetics (PK) of CTX340(From CTX340 infusion up to 12 months)