A Phase 2, Double-Blind Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Apitegromab in Subjects <2 Years Old With Spinal Muscular Atrophy (SMA)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 27
- 主要终点
- Evaluate the PK of apitegromab in subjects <2 years old with SMA
研究概览
简要总结
This double-blind, Phase 2, multiple-dose study will be conducted to evaluate the PK/PD, efficacy, safety, and tolerability of apitegromab in subjects <2 years old with 5q autosomal recessive SMA who have delayed motor milestones for their age attributed to SMA at the discretion of the Investigator or a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score <55.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Sponsor, the subject's caregiver, Investigators, and site personnel, with the exception of the designated unblinded personnel (eg, site Pharmacist), will be blinded to the treatment assignment.
入排标准
- 年龄范围
- — 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is <2 years old at the time of the informed consent
- •Had a gestational age of ≥35 weeks and gestational body weight ≥2.0 kg at birth
- •Has confirmed diagnosis of 5q autosomal recessive SMA
- •Has confirmed presence of SMN2 gene copy(ies)
- •Must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam)
- •Body weight for age is no less than 1st percentile based on the WHO Child Growth Standards at the Screening Visit
- •Has delayed motor milestones for age attributed to SMA at the discretion of the Investigator or a CHOP-INTEND score <55
排除标准
- •Nutritional status that is not anticipated to be stable throughout the study or medical necessity for a gastric feeding tube, where most feeds are administered by this route
- •Major orthopedic issues such as severe scoliosis or severe contractures or interventional procedure, including spine or hip surgery, which is considered to have the potential to substantially limit the ability of the subject to be evaluated on any motor function outcome measures, within 6 months before Screening or anticipated during the study
- •Any other physical limitations (eg, the subject requires cast for contractures) that would prevent the subject from undergoing motor function outcome measures throughout the study.
研究组 & 干预措施
Apitegromab high dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Nusinersen (Drug)
Apitegromab high dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Risdiplam (Drug)
Apitegromab low dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Apitegromab (Drug)
Apitegromab high dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Apitegromab (Drug)
Apitegromab low dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Nusinersen (Drug)
Apitegromab low dose + SMN Therapy
Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period.
Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
干预措施: Risdiplam (Drug)
结局指标
主要结局
Evaluate the PK of apitegromab in subjects <2 years old with SMA
时间窗: 52 Weeks
Apitegromab concentrations in serum
Evaluate the PD of apitegromab in subjects <2 years old with SMA
时间窗: 52 Weeks
Total latent myostatin concentrations in serum
Evaluate the motor function outcomes (ie, efficacy) due to apitegromab treatment
时间窗: 48 Weeks
Change from baseline in the raw score of the Bayley Scale of Infant and Toddler Development, Fourth Edition - Gross Motor Subscale (BSID-4 GMS) at 48 weeks. BSID-4 GMS is a standardized assessment commonly used to evaluate development across 5 domains in infants and young children. It consists of 58 items, scored from 0 to 2 for each item, with higher scores indicating better gross motor development.
Evaluate the motor function outcomes (ie, efficacy) due to apitegromab treatment
时间窗: 48 Weeks
Change from baseline in the raw score of the Bayley Scale of Infant and Toddler Development, Fourth Edition - Gross Motor Subscale (BSID-4 GMS) at 48 weeks. BSID-4 GMS is a standardized assessment commonly used to evaluate development across 5 domains in infants and young children. It consists of 58 items, scored from 0 to 2 for each item, with higher scores indicating better gross motor development.
Evaluate the PK of apitegromab in subjects <2 years old with SMA
时间窗: 52 Weeks
Apitegromab concentrations in serum
Evaluate the PD of apitegromab in subjects <2 years old with SMA
时间窗: 52 Weeks
Total latent myostatin concentrations in serum
次要结局
- Assess the safety and tolerability of apitegromab administered to subjects receiving an SMN therapy(52 Weeks)
- Assess the safety and tolerability of apitegromab administered to subjects receiving an SMN therapy(52 Weeks)