A Phase 1/2 Intracerebroventricular and Intravitreal Administration of NGN-101 for Treatment of Neuronal Ceroid Lipofuscinosis (NCL) Subtype 5 (CLN5) Disease
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
- Incidence of Serious Adverse Events (SAEs)
研究概览
简要总结
This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease.
详细描述
The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (CLN5) in subjects with CLN5 Batten disease. The study treatment will be delivered via intracerebroventricular (ICV) and intravitreal (IVT) injection on the same day. Each participant will be followed for safety and efficacy for 5 years after treatment. Efficacy assessments in this study will evaluate motor, language, visual and cognitive function.
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
- 3 Years 至 9 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age from 3 to 9 years (Child)
- •Molecular genetic diagnosis of the CLN5 gene
- •Confirmed clinical diagnosis of CLN5 disease
- •Impaired motor and/or language function and/or impaired visual acuity
- •Written informed consent from parent or legal guardian and assent from study participant, if appropriate
- •Able to comply with protocol required assessments (laboratory sample collection, lumbar puncture (LP), nerve conduction studies (NCS), magnetic resonance imaging (MRI), etc.), which may require sedation or general anesthesia
- •Able to walk with or without assistance (assistance may include a walker, braces, or with one hand held)
- •Agree to reside within a 1-hour drive of the study site for at least 6 months following treatment (or a safely drivable distance for the study participant and caregivers according to investigator's discretion)
排除标准
- •Has another neurologic disease or illness that may have caused cognitive decline before study entry
- •Known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides CLN5
- •Any active infections or severe infections within the 30 days prior to study treatment administration
- •Presence of a concomitant medical condition that precludes intracerebroventricular (ICV) injection, lumbar puncture (LP), or use of anesthetics needed for study-related procedures
- •Presence of any concomitant medical conditions that preclude intravitreal (IVT) administration
- •Has status epilepticus that lasts longer than 5 minutes or having more than 1 seizure within a 5-minute period, without returning to a normal level of consciousness between episodes within 12 weeks before study treatment
- •Total anti-AAV9 antibody titer greater than 1:400
- •Any anticipated need for major surgery in the next 24 months
- •Participation in an Investigational New Drug, Investigational Device Exemption, or equivalent clinical study in the past 6 months
- •Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
- •Participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the study participant is enrolled in this study with the exception of sister studies sponsored by Neurogene
- •History of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 3 months
- •Use of prohibited medications
- •Immunizations of any kind in the 45 days prior to study treatment
- •Requiring daytime or nighttime ventilatory support at the time of Screening
- •Any item which would exclude the study participant from being able to undergo brain magnetic resonance imaging (MRI) according to local institutional policy
- •Known allergies or hypersensitivities to the required immunosuppression regime
研究组 & 干预措施
Cohort 3
The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt).
干预措施: NGN-101 (Genetic)
Cohort 2
The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).
干预措施: NGN-101 (Genetic)
Cohort 1
The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).
干预措施: NGN-101 (Genetic)
结局指标
主要结局
Incidence of Serious Adverse Events (SAEs)
时间窗: 5 years (multiple visits)
Incidence, type, severity, and frequency of SAEs
Incidence of clinical laboratory abnormalities
时间窗: 5 years (multiple visits)
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Incidence of Treatment Emergent Adverse Events (TEAEs)
时间窗: 5 years (multiple visits)
Incidence, type, severity, and frequency of TEAEs
Incidence of new nerve conduction study (NCS) abnormalities
时间窗: 5 years (multiple visits)
Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Incidence of new physical and neurologic exam abnormalities
时间窗: 5 years (multiple visits)
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
次要结局
- Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)(5 years (multiple visits))
- Change in Unified Batten Diseases Rating Scale (UBDRS)(5 years (multiple visits))
- Change in color vision(5 years (multiple visits))
- Change in Hamburg Scale, Motor and Language domain scores(5 years (multiple visits))
- Change in visual acuity measurements(5 years (multiple visits))
- Change in Caregiver global impression of change(5 years (multiple visits))