An Open-label Study to Assess the Safety and Tolerability of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 18
- 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
The primary objective of this study is to examine the safety and tolerability of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA) who previously participated in ISIS 396443-CS1 (NCT02865109). The secondary objective was to examine the plasma pharmacokinetics of a single dose of ISIS 396443 administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS1.
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
- 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 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical signs attributable to Spinal Muscular Atrophy
- •Satisfactory completion of dosing and all study visits in ISIS 396443-CS1 (NCT01494701) with an acceptable safety profile, per Investigator judgement.
- •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
- •Have any new or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study.
- •Dosing in ISIS 396443-CS1 (NCT01494701) within 270 days (9 months) of screening, or longer ago than 450 days (15 months)
- •Dosing in ISIS 396443-CS2 (NCT01703988)
- •Hospitalization for surgery (i.e. scoliosis surgery) or pulmonary event within 2 months of screening or planned during the duration of the study
- •Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy any time during the screening period
- •Clinically significant abnormalities in hematology or clinical chemistry parameters
- •Treatment with investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Treatment with valproate or hydroxyurea within 1 months of screening. Any history of gene therapy or cell transplantation
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
nusinersen
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 24 Weeks
Number of participants with clinically significant physical examination abnormalities
时间窗: Up to 24 Weeks
Number of participants who use concomitant medications
时间窗: Up to 24 Weeks
Number of participants with clinically significant neurological examination abnormalities
时间窗: Up tp 24 Weeks
Number of participants with clinically significant vital sign abnormalities
时间窗: Up to 24 Weeks
Number of participants with clinically significant weight abnormalities
时间窗: Up to 24 Weeks
Number of participants with clinically significant laboratory parameters
时间窗: Up to 24 Weeks
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
时间窗: Up to 24 Weeks
次要结局
- PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)(Plasma at 1, 2, 4 and 6 hours after dosing)
- 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)(Plasma at 1, 2, 4 and 6 hours after dosing)
- PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)(Plasma at 1, 2, 4 and 6 hours after dosing)
- PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible(Plasma at 1, 2, 4 and 6 hours after dosing)