Onasemnogene Abeparvovec: ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 36
- 主要终点
- Change from baseline in HFMSE for independently ambulatory participants
研究概览
简要总结
The primary purpose is to address critical evidence in the treatment landscape for Spinal Muscular Atrophy (SMA), specifically focusing on the intrathecal formulation of onasemnogene abeparvovec-brve (ITVISMA®). U.S. Pragmatic Multicenter Study (STREAM).
详细描述
STREAM is a prospective, multicentre cohort study that will follow U.S. participants with genetically confirmed SMA who receive a single, intrathecal dose of onasemnogene abeparvovec-brve. All eligible participants are enrolled prior to therapeutic injection. No randomisation, blinding, or placebo control is employed; instead, each participant acts as his or her own baseline comparator. This study will use an exploratory external cohort of patients matched by age, clinical characteristics, treatment history and availability of at least 1 year of pre-treatment medical history. This patient cohort will be based on a database of retrospectively collected electronic medical records data and will be used descriptively to contextualize study outcomes. Bias is minimised through pre-specified endpoints, uniform rater training on motor-function scales, and a detailed statistical analysis plan that stipulates handling of missing data and intercurrent events in advance.
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 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A participant will be enrolled in STREAM only if all the following conditions are met:
- •The participant has a genetically confirmed diagnosis of SMA (biallelic SMN1 deletion or mutation).
- •He or she is ≥ 2 years of age on the day of the intrathecal injection.
- •The treating Investigator intends to administer within the current episode of care, a single dose of ITVISMA® (1.2 × 10¹⁴ vg) in routine U.S. practice after written informed consent obtained.
- •One of the following functional categories applies at screening:
- •independently ambulatory child/adolescent 2 - <18 years; or
- •independently ambulatory adult (≥ 18 years).
- •non-ambulatory (includes walkers with assistance) adult > 18 years with entry level RULM at baseline
- •At least 1 year of pre-treatment medical history, including motor-function documentation, can be retrieved from the site electronic record.
排除标准
- •A participant will be excluded if any of the following conditions apply:
- •Contraindication for lumbar puncture as determined by the investigator (e.g., spinal anatomy that precludes safe lumbar puncture)
- •An uncontrolled acute illness, active infection, febrile illness or acute medical condition, within 30 days prior to dosing
- •Inability to tolerate corticosteroids administered by mouth or gastrostomy tube
- •Current participation in another interventional clinical trial that would interfere with the objectives or endpoints of STREAM. Note: participation in observational cohort studies or non-interventional studies in which the participant does not receive treatment or undergo procedures which may compromise this study data integrity may be allowed following Sponsor approval
- •Planned relocation or any circumstance that is likely to prevent completion of the minimum 12-month follow-up.
- •Other protocol inclusion, exclusion criteria may apply.
研究组 & 干预措施
Onasemnogene Abeparvovec-brve
Participants with spinal muscular atrophy, including:
- independently ambulatory children/adolescents (≥ 2 years to < 18 years);
- independently ambulatory adults (≥ 18 years);
- Non-ambulatory adults (≥ 18 years)
干预措施: Onasemnogene Abeparvovec-brve (Drug)
结局指标
主要结局
Change from baseline in HFMSE for independently ambulatory participants
时间窗: Baseline, 6, 12, 18 and 24 months
The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Change from baseline in RULM for non-ambulatory (including walkers with assistance) participants
时间窗: Baseline, 6, 12, 18 and 24 months
The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in independent ambulatory and non-ambulatory (including walkers with assistance) individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
次要结局
- Daily hours of respiratory support (none, non-invasive ventilation, invasive ventilation)(Baseline, up to 24 months)
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(up to 5 years)
- Modified SMA Functional Rating Scale (SMA-FRS) for independently ambulatory participants (≥ 18 years of age) and non-ambulatory particpants(Baseline, 6, 12, 18 and 24 months and Years 3, 4, and 5)
- Cobb angle(Baseline, up to 24 months)
- Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) for independently ambulatory participants (<18 years of age)(Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5)
- Subgroup outcomes: Hammersmith Functional Motor Scale Expanded (HFMSE)(Baseline, 6, 12, 18 and 24 months)
- Subgroup outcomes: Revised Upper Limb Module (RULM)(Baseline, 6, 12, 18 and 24 months)
- Frequency of hospitalizations emergency department visits, outpatient visits, respiratory interventions and nutritional support interventions(Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5)
- Duration of hospitalizations emergency department visits, outpatient visits, respiratory interventions and nutritional support interventions(Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5)
- Joint-range limitation measured by goniometer(Baseline, up to 24 months)
- Nutritional-support category (oral, gastrostomy feeds, total parenteral nutrition)(Baseline, up to 24 months)
- 6-Minute Walk Test (6MWT) for ambulatory patients(Baseline, Months 6, 12, 18, and 24)