A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 34
- 主要终点
- Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment
研究概览
简要总结
This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered in pediatric participants with SMA and 2 SMN2 copies who previously received onasemnogene abeparvovec and experience a plateau or decline in function. Participants to be enrolled are children <2 years of age genetically diagnosed with SMA.
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
- 3 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •<2 years of age at the time of informed consent
- •Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
- •Confirmed presence of two SMN2 gene copies as documented through laboratory testing
- •Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
- •Has received onasemnogene abeparvovec for SMA no less than 13 weeks prior to enrollment
- •If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration.
- •In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 26 weeks or less) documented by 2 individual time points in the functions as follows: swallowing AND one additional function/ability (respiratory, motor function, other) per appropriate expectation.
排除标准
- •Previous or current enrolment in investigational study prior to initiation of study treatment
- •Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
- •Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
- •Concomitant or previous use of an anti-myostatin agent
- •Participants requiring invasive ventilation or tracheostomy
- •Presence of feeding tube and an OrSAT score of 0
- •Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
- •Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration.
研究组 & 干预措施
Risdiplam
Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled.
干预措施: Risdiplam (Drug)
结局指标
主要结局
Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment
时间窗: Baseline, Week 72
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.
Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment
时间窗: Baseline, Week 72
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.
次要结局
- Percentage of Participants With Adverse Events(Up to 120 weeks)
- Percentage of Participants With Serious Adverse Events(Up to 120 weeks)
- Percentage of Participants With Treatment Discontinuation Due to Adverse Events(Up to 120 weeks)