An Exploratory Clinical Trial to Evaluate the Tolerability and Safety of VGN-R08b Via Intracerebroventricular Injection in Patients With Type II Gaucher Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
研究概览
简要总结
This exploratory trial is to prove the tolerability and safety of VGN-R08b to treat infants with type II Gaucher disease.
详细描述
Gaucher disease (GD) is an autosomal recessive genetic metabolic disorder. Due to the mutation of Glucocerebrosidase gene (GBA1), the activity of glucocerebrosidase (GCase) in the lysosome of the body is reduced, causing its substrate glucocerceramide to be accumulated in macrophage lysosomes in the liver, spleen, bone, lung, brain and eyes. Type II, acute neuropathy, with extensive and severe visceral involvement, usually develops within the first year of life, and most children die before the age of 2. VGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular.
This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R08b treatment for patients with type II Gaucher disease.
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
- 0 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants with age of ≤24 months.
- •Historical diagnosis of Gaucher disease confirmed by GCase enzyme activity test, and with GBA1 biallelic mutations.
- •Neurological signs and/or symptoms consistent with diagnosis of GD
- •Parent(s)/legal guardian(s) of subject must give their consent for subject to enroll in the study.
- •Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
排除标准
- •Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound study objectives.
- •Achieved independent gait.
- •Severe visceral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
- •Clinically active infection (including HIV, HBV, HCV or syphilis).
- •For those receiving enzyme replacement therapy and/or substrate reduction therapy and/or ambroxol for Gaucher disease, stable treatment ≤2 months before enrollment.
- •Use of strong inhibitors or inducers of cytochrome CYP3A4 or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
- •Any type of prior gene or cell therapy.
- •Immunizations (live vaccines) in the prior 4 weeks.
- •Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical preparations for dermatological conditions are allowed).
- •Patients with anti-AAV9 neutralizing antibody titer over 1:
- •Brain MRI (magnetic resonance imaging) showing clinically significant abnormality considered to prevent intracisternal injection.
- •Contraindication to sedation during surgery or imaging studies (PET).
- •Presence of other significant medical conditions that would create an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
研究组 & 干预措施
type II Gaucher disease
This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase
干预措施: VGN-R08b (Drug)
结局指标
主要结局
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
时间窗: Week 52
Adverse Events (AEs), Serious Adverse Events (SAEs)
次要结局
- Long-term safety follow-up(Up to Year 5)
- Survival ratio at age of 24 months(Baseline until event, or reach the age of 24 months, Up to Year 5)
- Changes in the activity of glucose cerebroside lipase (GCase)(Up to Year 5)
- Changes in the activity of glucose sphingosine (Lyso GL1) levels in peripheral blood and CSF after medication(Up to Year 5)
- Changes in the activity of glucose cerebroside (GC) levels(Up to Year 5)
- Immunogenicity(26 weeks)
- Changes in the genomic level of VGN-R08b vector in peripheral blood after medication(26 weeks)