An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease.
详细描述
This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease.
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
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
- •Male or female ≥ 18 years of age
- •Pathogenic GLA mutation consistent with Fabry Disease
- •Confirmed diagnosis of classic or late-onset Fabry disease
- •Individuals on ERT must be on a stable dose for at least 6 months (and a minimum of 12 months total exposure) prior to study enrollment
- •Agree to use highly effective contraception
排除标准
- •Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
- •eGFR <45 mL/min/1.73 m2
- •Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
- •HIV, active or chronic hepatitis B or C,
- •Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control
- •History of stroke or transient ischemic attack within the last 12 months, or other significant thromboembolic disease history (e.g. pulmonary embolism)
- •Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
- •Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the last 12 months.
- •Moderately severe to severe cardiovascular disease or uncontrolled hypertension
- •Left ventricular ejection fraction of <45% on echocardiogram (ECHO)
- •Currently receiving investigational drug, device or therapy or having ever received gene therapy
- •History of infusion related response to ERT or any adverse reaction leading to ERT discontinuation
- •History of cancer within 2 years (exceptions include non-melanoma skin cancer, localized prostate cancer treated with curative intent)
- •Pregnant or breast-feeding
结局指标
主要结局
Incidence and severity of adverse events
时间窗: 1 year
Safety and tolerability of 4D-310 following a single IV dose, as assessed by incidence and severity of adverse events, serious adverse events and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters
次要结局
- Change from baseline in serum AGA activity(1 year)
- Change from baseline serum globotriaosylsphingosine (lysoGb3)(1 year)