Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 17
- 主要终点
- Overview of Treatment-emergent Adverse Events by Age Subgroup
研究概览
简要总结
This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to <18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to <6 years, and 6 to <18 years).
详细描述
Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.
Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B 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.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SMA diagnosis
- •Aged 2 to < 18 years
- •Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
- •Must have symptoms of SMA as defined in the protocol
排除标准
- •Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
- •Clinically significant abnormalities in test results during screening
- •Contraindications for lumbar puncture procedure
- •At Baseline, participants are excluded if they received:
- •nusinersen (Spinraza®) or
- •risdiplam (Evrysdi®) within a defined timeframe
- •Vaccinations 2 weeks prior to administration of OAV101
- •Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
- •Presence of an infection or febrile illness up to 30 days prior to administration of OAV101
- •Requiring invasive ventilation
研究组 & 干预措施
OAV-101
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
干预措施: OAV101 (Genetic)
结局指标
主要结局
Overview of Treatment-emergent Adverse Events by Age Subgroup
时间窗: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)
时间窗: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup
时间窗: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (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. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. An adverse event of special interest (AESI) is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Transient thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, signs and symptoms that may be suggestive dorsal root ganglia toxicity, and new malignancies.
次要结局
- Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)(Baseline, Week 52)
- Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means(Baseline, Week 52)
- Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)(Baseline, Week 52)
- Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means(Baseline, Week 52)
- Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)(Baseline, Week 52)
- Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means(Baseline, Week 52)