A Long-Term Extension Study of Nusinersen (BIIB058) Administered at Higher Doses in Participants With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 115
- 试验地点
- 39
- 主要终点
- Number of Participants With Shifts from Baseline in Vital Signs
研究概览
简要总结
In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study is an extension study and will enroll only those participants who have completed treatment in the parent study, 232SM203.
The main goal of the study is to learn about the long-term safety of nusinersen. The main questions researchers want to answer are:
- How many participants have adverse events and serious adverse events during the study?
- How do the results of electrocardiograms (ECGs), vital signs, and laboratory tests including blood and urine tests change after treatment?
- How many participants have a low platelet count after treatment?
- How many participants had a change in the time it took for their heart to recharge between beats after treatment?
- How does each participant's height and other measures of growth change after treatment?
- How much do the results of neurological exams that check movement, reflexes, and brain function change after treatment?
Researchers will also learn about the effect of nusinersen on mobility using various tests. They will study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing.
The 232SM302 study will be done as follows:
- Participants will be screened to check if they can join the study.
- Participants will receive their 1st dose of nusinersen in this study about 4 months after their final dose in the parent study.
- Each participant will receive nusinersen once every 4 months during the treatment period.
- Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
- The treatment period will last for up to 64 months (1921 days).
- There will be a follow-up safety period that lasts from 4 to 8 weeks.
- In total, participants will have up to 19 study visits. Participants will stay in the study for close to 6 years.
详细描述
The primary objective of this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566).
The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol
排除标准
- •Treatment with another investigational therapy or enrollment in another interventional clinical study
- •Treatment with an approved therapy for SMA after the Day 302 Visit of Study 232SM203 (NCT04089566)
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
BIIB058 50/28 mg (Prior Maintenance Dose 12 mg)
Participants who received maintenance dose of 12 mg nusinersen in study 232SM203 (NCT04089566), will receive loading dose of 50 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.
干预措施: Nusinersen (Drug)
BIIB058 28 mg (Prior Maintenance Dose 28 mg)
Participants who received maintenance dose of 28 milligrams (mg) nusinersen in study 232SM203 (NCT04089566), will receive maintenance dose of 28 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.
干预措施: Nusinersen (Drug)
结局指标
主要结局
Number of Participants With Shifts from Baseline in Vital Signs
时间窗: Up to Day 1921
Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
时间窗: Up to Day 1921
Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
时间窗: Up to Day 1921
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to Day 1921
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.
Change from Baseline in Growth Parameters
时间窗: Up to Day 1921
Growth parameters will be assessed by measuring body length or height (if feasible and appropriate), ulnar length (all participants), and head circumference, chest circumference, and arm circumference (all participants 3 years of age and younger) in centimeters.
Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
时间窗: Up to Day 1921
Change from Baseline in Prothrombin Time (PT)
时间窗: Up to Day 1921
Change from Baseline in International Normalized Ratio (INR)
时间窗: Up to Day 1921
Change from Baseline in Urine Total Protein
时间窗: Up to Day 1921
Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age
时间窗: Up to Day 1921
For participants 2 years of age and younger, the Hammersmith Infant Neurological Exam (HINE) Sections 1 and 3 will be conducted. This standard examination (developed by \[Dubowitz and Dubowitz 1981\]) is a quantitative scorable method for assessing the neurological development of infants between 2 and 24 months of age. The examination includes assessment of cranial nerve functions, posture, movements, tone, and reflexes. The HINE Section 1 form utilized in ONWARD contains 26 items and the Section 3 form utilized contains 3 items. For HINE Section 1 items, each item is scored 0-3. For HINE Section 3 items, scoring is variable (1-4, 1-5, or 1-6). Higher scores indicate better neurological function.
Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age
时间窗: Up to Day 1921
For all participants \>2 years of age, standard neurological examinations, which include assessments of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes, will be conducted.
Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
时间窗: Up to Day 1921
Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec
时间窗: Up toDay 1921
次要结局
- Percentage of Time Spent on Ventilation(Up to Day 1921)
- Percentage of HINE Section 2 Motor Milestone Responders(Up to Day 1921)
- Time to Death or Permanent Ventilation(Up to Day 1921)
- Change From Baseline in Plasma Levels of Neurofilament (NF)(Up to Day 1921)
- Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score(Up to Day 1921)
- Change from Baseline in Revised Upper Limb Module (RULM) Score(Up to Day 1921)
- Total Number of New World Health Organization (WHO) Motor Milestones(Up to Day 1921)
- Number of Participants Who Used Respiratory Support, by Type(Up to Day 1921)
- Number of Hours Per Day of Respiratory Support(Up to Day 1921)
- Number of Days That Respiratory Support Is Used(Up to Day 1921)
- Time to Death (Overall Survival)(Up to Day 1921)
- Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score(Up to Day 1921)
- Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones(Up to Day 1921)