NCT04693598进行中（未招募）1 期
A Phase 1/2 Clinical Study of Intravenous Gene Transfer With an AAVrh10 Vector Expressing GALC in Krabbe Subjects Receiving Hematopoietic Stem Cell Transplantation (RESKUE)
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Safety as assessed by HSCT incident of engraftment.
研究概览
简要总结
This is a nonblinded, non-randomized dose escalation study of intravenous AAVrh10 after hematopoietic stem cell transplantation (HSCT) in which subjects will receive standard of care hematopoietic cell transplantation for Krabbe disease, followed by a single infusion of an adeno-associated virus gene therapy product. Extensive natural history subjects will be used to compare as control group.
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
- 1 Day 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of infantile Krabbe disease, characterized by the following criteria outlined below:
- •Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING:
- •Elevated psychosine levels predictive of infantile disease onset by DBS; OR
- •Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
- •Two GALC mutations predictive to result in infantile onset phenotype.
- •Age at the time of screening: 1 day to 12 months
- •Participant has been deemed eligible for treatment with HSCT (standard of care) and a fully myeloablative reduced intensity/toxicity conditioning regimen (RIC/RTC) is/has been used
- •Participant's parents or legal guardian consents to participate in the study and provides informed consent according to IRB guidelines prior to any study procedures being performed
- •Parent(s) and/or legal guardian able to comply with the clinical protocol
- •Participant must have adequate organ function at time of screening as measured by:
- •Creatinine ≤ 1.5x upper limit of age appropriate normal and creatinine clearance ≥ 60 mL/min/1.73 m2
- •Hepatic transaminases (ALT/AST) ≤ 2x age related upper limit of normal
- •Ejection fraction of > 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension
- •Pulmonary evaluation testing demonstrating resting pulse oximeter > 95% on room air
- •Coagulation tests within 110% of normal ranges for age. (PT/INR and PTT)
排除标准
- •History of prior treatment with a gene therapy product
- •Presence of major congenital anomaly or any other condition that affects neurodevelopmental function
- •Presence of any neurocognitive deficit or brain damage not attributable to Krabbe disease
- •Active aspiration
- •Signs of active infection or disease from cytomegalovirus, adenovirus or other viruses
- •HIV positive
- •Uncontrolled and progressive bacterial or fungal infection
- •Presence of any contraindication for MRI
- •Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
- •Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study
- •Ongoing veno-occlusive disease (VOD) as determined by liver ultrasound (moderate ascites and static or retrograde portal vein flow) the day before FBX-101 infusion.
研究组 & 干预措施
Cohort 1 - Low Dose FBX-101 (aka AAVrh.10-GALC)
Experimental
Participants will receive a single infusion at the lower dose (N=3 participants)
干预措施: FBX-101 (Biological)
Cohort 2 - High Dose FBX-101 (aka AAVrh.10-GALC)
Experimental
Participants will receive a single infusion at the higher dose (N=3 participants)
干预措施: FBX-101 (Biological)
结局指标
主要结局
Safety as assessed by HSCT incident of engraftment.
时间窗: 24 months
Safety as assessed by incidence and severity of adverse events and serious adverse events that are attributed to FBX-101.
时间窗: 24 months
次要结局
- Efficacy as assessed by improvement of probability to achieve independent sitting compared to untreated patients or those receiving HSCT only.(12 months and 24 months)
- Efficacy as assessed by improvement of gross motor function as measured by Peabody Developmental Motor Scale 2nd Edition (PDMS-2) above a functional age equivalent of 12 months compared to untreated patients or those receiving HSCT only(24 months)
研究者
研究点 (2)
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