A Phase IIIb, Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Gene Replacement Therapy With Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 14
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
研究概览
简要总结
To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.
详细描述
This was an open-label, single arm, multi-center study designed to evaluate the safety, tolerability and efficacy of OAV101 in participants with SMA who weigh ≥ 8.5 kg and ≤ 21 kg. The study aimed to enroll approximately 24 to 30 participants, with approximately 6 to 10 participants across each of 3 weight brackets (8.5 to 13 kg, >13 to 17 kg, >17 to 21 kg).
Eligible participants received a single administration of OAV101 at the approved dose of 1.1e14 vg/kg on Day 1 (Treatment period), and were followed for a period of 12 months.
Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101 on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.
After study completion, eligible participants could enroll into a Long Term follow-up study to collect additional safety and efficacy data. (COAV101A12308 (NCT05335876) https://classic.clinicaltrials.gov/ct2/show/NCT05335876?term=COAV101A12308\&draw=2\&rank=1))
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
时间窗: Up to Month 12
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)
Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change from baseline in vital signs measurements - oxygen saturation level (%). Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.
Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket
时间窗: Up to Month 12
Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy. These were assessed by the investigator.
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure
时间窗: 12 months
Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg). Systolic Blood Pressure-Low:\<=5th percentile of the age(Any Age), High:\>=90th percentile of the age, gender, and height group (\<18 yrs). Diastolic Blood Pressure-High:\>=90th percentile of the age, gender, and height group(\<18 yrs).
Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)
时间窗: Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Change from baseline in vital signs measurements - Pulse Rate (beats/min
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature
时间窗: 12 months
Change from baseline in vital signs measurements - temperature (degrees Celsius) Temperature-Low:\<=35ºC(Any Age),High:\>=38.4ºC(\<18 yrs).
次要结局
- Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.(Baseline, Week 26 and Week 52)
- Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.(Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52)
- Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age(Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52)