NCT02386553已完成2 期
An Open-Label Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Subjects With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 25
- 试验地点
- 21
- 主要终点
- Time to Death or Respiratory Intervention
研究概览
简要总结
The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic 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
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 0 Weeks 至 6 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≤ 6 weeks at first dose.
- •Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
- •Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
- •Ulnar compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
- •Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
- •Meet additional study related criteria.
排除标准
- •Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
- •Any clinical signs or symptoms at Screening or immediately prior to the first dosing (Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.
- •Clinically significant abnormalities in hematology or clinical chemistry parameters.
- •Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
- •Meet additional study related criteria.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Nusinersen
Experimental
Nusinersen administered as an intrathecal injection
干预措施: Nusinersen (Drug)
结局指标
主要结局
Time to Death or Respiratory Intervention
时间窗: Screening up to Day 2891
The time was the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention was defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.
次要结局
- Proportion of Participants Developing Clinically Manifested Spinal Muscular Atrophy (SMA)(At 13 and 24 months of age)
- Percentage of Participants Who Attained Motor Milestones Assessed as Part of the Hammersmith Infant Neurological Examination (HINE)(Day 700)
- Percentage of Participants Alive(Up to 8 years of age)
- Change From Baseline in Head to Chest Circumference Ratio(Baseline, Day 2891)
- Change From Baseline in Vital Signs (Heart Rate)(Baseline, Day 2891)
- Percentage of Participants Who Attained Motor Milestones as Assessed by World Health Organization (WHO) Criteria(Baseline up to Day 2891)
- Change From Baseline in Arm Circumference(Baseline, Day 2891)
- Change From Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale(Baseline, Day 2891)
- Change From Baseline in Head Circumference(Baseline, Day 2891)
- Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)(Baseline, Day 2160)
- Change From Baseline in Weight for Age(Baseline, Day 2891)
- Change From Baseline in Weight for Length(Baseline, Day 1849)
- Change From Baseline in Vital Signs (Temperature)(Baseline, Day 2891)
- Change From Baseline in Chest Circumference(Baseline, Day 2891)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From the signing of the informed consent form (ICF) up to the end of the study (up to Day 2891))
- Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)(Baseline up to Day 2891)
- Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)(Baseline up to Day 2891)
- Number of Participants With Shifts From Baseline in Coagulation Parameters [Activated Partial Thromboplastin Time (aPTT)](Baseline up to Day 2891)
- Number of Participants With Shifts From Baseline in Coagulation Parameters [Prothrombin Time (PT)](Baseline up to Day 2891)
- Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)(Baseline up to Day 2891)
- Number of Participants With Shifts From Baseline in Coagulation Parameters [International Normalized Ratio (INR)](Baseline up to Day 2891)
- Change From Baseline in Vital Signs (Blood Pressure)(Baseline, Day 2891)
- Change From Baseline in Vital Signs (Respiratory Rate)(Baseline, Day 2891)
- Percentage of Participants With Clinically Significant Shifts in Electrocardiograms (ECG) Abnormalities(Baseline up to Day 2891)
- Cerebrospinal Fluid (CSF) Concentration of Nusinersen(Predose on Days 1, 15, 29, 64, 183, 302, 421, 540, 659, 778, 897, 1016, 1135, 1254, 1373, 1492, 1611, 1730, 1849, 1968, 2087, 2206, 2325, 2444, 2563, 2682, 2801)
- Plasma Concentration of Nusinersen(Predose on Days 64, 183, 302, 421, 540, 659, 778, 897, 1016, 1135, 1254, 1373, 1492, 1611, 1730, 1849, 1968, 2087, 2206, 2325, 2444, 2563, 2682, 2801 and 4-hour post-dose on Day 1)
- Number of Participants With Neurological Examination Abnormalities Reported as AEs(From the signing of the ICF up to the end of the study (up to Day 2891))
研究者
研究点 (21)
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