An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
研究概览
简要总结
This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).
详细描述
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc.
In August 2016, sponsorship of the trial was transferred to Biogen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
- •Clinical signs attributable to Spinal Muscular Atrophy (SMA)
- •Able to complete all study procedures, measurements and visits and parent/participant has adequately supportive psychosocial circumstances, in the opinion of the investigator
- •Estimated life expectancy > 2 years from Screening
- •Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedure
排除标准
- •Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
- •Presence of a gastric feeding tube
- •Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
- •Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
- •Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
- •History of brain or spinal cord disease that would interfere with LP procedures or cerebrospinal fluid (CSF) circulation
- •Presence of an implanted shunt for the draining of CSF or an implanted Central Nervous System (CNS) catheter
- •History of bacterial meningitis
- •Clinically significant abnormalities in hematology or clinical chemistry parameters
- •Treatment with another investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent whichever is longer. Any history of gene therapy or cell transplantation
- •Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the participant to undergo study procedures
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1 (n=6)
干预措施: nusinersen (Drug)
Cohort 2 (n=6)
干预措施: nusinersen (Drug)
Cohort 3 (n=6)
干预措施: nusinersen (Drug)
Cohort 4 (n=10)
干预措施: nusinersen (Drug)
结局指标
主要结局
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
时间窗: Up to 88 Days
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
时间窗: Up to 88 Days
PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible
时间窗: Plasma at 1, 2, 4 and 20 hours after dosing
Number of participants with clinically significant physical examination abnormalities
时间窗: Up to 88 Days
Number of participants with clinically significant laboratory parameters
时间窗: Up to 88 Days
Number of participants with clinically significant vital sign abnormalities
时间窗: Up to 88 Days
Number of participants with clinically significant weight abnormalities
时间窗: Up to 88 Days
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
时间窗: Up to 88 Days
PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
时间窗: Plasma at 1, 2, 4 and 20 hours after dosing
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
时间窗: Plasma at 1, 2, 4 and 20 hours after dosing
Number of participants with clinically significant neurological examination abnormalities
时间窗: Up to 88 Days
Number of participants who use concomitant medications
时间窗: Up to 88 Days
PK parameters of nusinersen: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf)
时间窗: Plasma at 1, 2, 4 and 20 hours after dosing
次要结局
未报告次要终点