Open-label, Single-arm, Multi-center Study of Intracerebral Administration of Adeno-associated Viral (AAV) Serotype rh.10 Carrying Human N-sulfoglucosamine Sulfohydrolase (SGSH) cDNA for Treatment of Mucopolysaccharidosis Type IIIA
试验速览
- 阶段
- 2 期
- 发起方
- LYSOGENE
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
研究概览
简要总结
MPS IIIA is predominantly a central nervous system disease causing cognitive disability, progressive loss of acquired skills, behavioral and sleep disturbance. LYS-SAF302 is a gene therapy which is intended to deliver a functional copy of the SGSH gene to the brain. This is a phase 2-3 study to assess the efficacy in improving or stabilizing the neurodevelopmental state of MPS IIIA patients.
详细描述
The study is interventional, single arm and multi-center. Evolution under treatment will be compared to expected natural evolution based on natural history studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
- •Cognitive DQ score on BSID-III: 50% and above
排除标准
- •Homozygous for the S298P mutation or non-classical severe form of MPS IIIA, based on investigator's judgement.
- •Participation in another gene or cell therapy clinical trial.
- •Past use of SGSH enzyme replacement therapy for a period exceeding 3 months. A washout period of at least 2 months is required prior to screening.
- •Current participation in a clinical trial of another investigational medicinal product.
- •History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery.
- •Any condition that would contraindicate treatment with immunosuppressants such as tacrolimus, mycophenolate mofetil or steroids.
研究组 & 干预措施
AAV SGSH gene therapy (LYS-SAF302)
One-time intracerebral administration of adeno-associated viral vector serotype rh10 containing the human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA.
干预措施: LYS-SAF302 (Drug)
结局指标
主要结局
Change from baseline in development quotient (DQ), compared to regression reported in natural history studies
时间窗: Month 6, 12, 18, 24
Development Quotient will be measured for each patient using one of two standard instruments, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), based on age and ability range. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which is computed as a ratio and expressed as a percentage using the development age (DA) score divided by the age at testing (\[development age score/chronological age\] × 100; range: 0 - 100, where high values are desirable).
次要结局
- Incidence and severity of treatment-emergent adverse events and serious adverse events throughout the study(Month 24)
- Change from baseline in total cortical grey matter volume and white matter volume on MRI(Month 12, 24)
- Change from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II)(Month 6, 12, 18, 24)
- Change in sleep pattern as measured by the Childrens Sleep Habits Questionnaire (CSHQ)(Month 6, 12, 18, 24)
- Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)(Month 12, 24)
- Change from baseline in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire(Month 12, 24)