A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.
详细描述
The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of iduronidase for the lifetime of an MPS I patient.
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 5 years of age
- •Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)
排除标准
- •Known to be unresponsive to ERT
- •Neutralizing antibodies to AAV 2/6
- •Serious intercurrent illness or clinically significant organic disease (unless secondary to MPS I)
- •Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2
- •Lack of tolerance to laronidase treatment with significant IARs or occurrence of anaphylaxis
- •Markers of hepatic dysfunction
- •Creatinine ≥ 1.5 mg/dL
- •Contraindication to the use of corticosteroids for immunosuppression
- •Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use (topical treatment allowed)
- •Participation in prior investigational drug or medical device study within the previous 3 months
- •Prior treatment with a gene therapy product
- •Elevated or abnormal circulating α-fetoprotein (AFP)
- •Weight <20 kg at Screening Visit
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: Up to 36 months after the SB-318 infusion
Number of Participants with Treatment-Emergent Adverse Events
次要结局
- Effect of SB-318 on IDUA Activity(Baseline and Month 36 after the SB-318 infusion)
- Effect of SB-318 on Urine Glycosaminoglycans (GAG) Levels(Baseline and 24 months after the SB-318 infusion)
- AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen(Up to 24 months after the SB-318 infusion)