Phase I/IIa Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Incidence And Severity Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a phase 1/2, open-label, single dose study to evaluate the safety and efficacy of AT-GTX-501 delivered intrathecally into the lumbar spinal cord region of participants with mild to moderate variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6 disease).
详细描述
This is an open-label, single-dose study of AT-GTX-501 administered by a single intrathecal injection. Safety and efficacy are evaluated over a 2 year period. The efficacy assessments in this study are to evaluate motor, language, visual, and cognitive function, as well as survival and other outcome measures. Participants are tested at baseline, receive AT-GTX-501 on Day 0, and return for visits on Days 7, 14, 21, and 30, and then every 3 months until Month 24. Following completion of this study, there is a long-term follow up study in which data will continue to be collected (Study AT-GTX-501-02 / NCT04273243).
For more information about this study, please contact Amicus Therapeutics Patient Advocacy at clinicaltrials@amicusrx.com or +1 609-662-2000.
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
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of vLINCL6 disease determined by genotype available at screening
- •A score of ≥ 3 on the quantitative clinical assessment of the Hamburg motor-language aggregate scale at screening
- •Aged ≥ 1 year
- •Ambulatory or able to walk with assistance
排除标准
- •Presence of another inherited neurologic disease, for example, other forms of Batten disease (also known as NCL) or seizures unrelated to vLINCL6 disease (participants with febrile seizures may be eligible at discretion of the investigator.)
- •Presence of another neurological illness that may have caused cognitive decline (for example, trauma, meningitis, hemorrhage) before screening
- •Active viral infection (includes human immunodeficiency virus or serology positive for hepatitis B or C)
- •Has received stem cell or bone marrow transplantation for vLINCL6 disease
- •Contraindications for intrathecal administration of the product or lumbar puncture, such as bleeding disorders or other medical conditions (for example, spina bifida, meningitis, or clotting abnormalities)
- •Contraindications for magnetic resonance imaging scans (for example, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
- •Episode of generalized motor status epilepticus within 4 weeks before the gene transfer visit (Visit 2)
- •Severe infection (for example, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the gene transfer visit (Visit 2) (Enrollment may be postponed.)
- •Has received any investigational medication within 30 days before the gene transfer visit (Visit 2)
- •Anti-AAV9 antibody titers > 1:50 as determined by enzyme-linked immunosorbent assay
- •Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with the protocol-required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability
- •Pregnancy any time during the study (Any female participant judged by the investigator to be of childbearing potential will be tested for pregnancy.)
- •Abnormal laboratory values from screening considered clinically significant (gamma glutamyl transferase > 3 times the upper limit of normal, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.8 mg/dL, hemoglobin < 8 or > 18 g/dL, white blood cells > 15,000 per cmm)
- •Family does not want to disclose participant's study participation with primary care physician and other medical providers.
- •History of or current chemotherapy, radiotherapy, or other immunosuppression therapy within the 30 days preceding screening (Corticosteroid treatment may be permitted at the discretion of the investigator.)
- •Has 2 consecutive abnormal liver tests at screening (> 2 times the upper limit of normal). Liver enzymes will be re-tested once if abnormal upon initial screening.
结局指标
主要结局
Incidence And Severity Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to 38.7 months
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device (medicinal products). An SAE is an AE occurring during any study phase (for example, baseline, treatment, or follow-up) that fulfils any of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; and results in a congenital anomaly/birth defect. All AEs that occurred after receipt of AT-GTX-501 are classified as TEAEs. A summary of serious and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.
次要结局
- Change From Baseline In Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) At Month 24(Screening (Day -30 up to -2) and Month 24)
- Change From Baseline In Development Profile-3 At Month 24(Screening (Day -30 up to -2) and Month 24)
- Change From Baseline In Hamburg Motor And Language Scores at Month 24(Screening (Day -30 up to -2) up to Month 24)
- Change From Baseline In Unified Batten Disease Rating Scale (UBDRS) Scores At Month 24(Screening (Day -30 up to -2) and Day 30 up to Month 24)
- Change From Baseline In Mullen (Age-Equivalent) Scales Of Early Learning At Month 24(Screening (Day -30 up to -2) and Month 24)
研究者
Emily de los Reyes
Dr. Emily De Los Reyes
Nationwide Children's Hospital