An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 292
- 试验地点
- 46
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective is to evaluate long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with Spinal Muscular Atrophy (SMA) who previously participated in investigational studies of nusinersen. The secondary objective is to examine the long-term efficacy of nusinersen administered by IT injection to participants with SMA who previously participated in investigational studies of nusinersen.
详细描述
This study was initiated and the protocol was registered by Ionis Pharmaceuticals, Inc.
In August 2016, Biogen assumed responsibility for this study.
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
盲法说明
During the blinded loading period, the following participants will be masked:
- Key site personnel (Investigator, Study Coordinator, and Outcomes Assessors)
- Participant
- The sponsor
After the loading period has been completed, subsequent doses will be unblinded.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
- •Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks
排除标准
- •Have any condition or worsening 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
- •Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
- •Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- •Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Group 1
Participants transitioned from ISIS 396443-CS3B (NCT02193074)
干预措施: nusinersen (Drug)
Group 2
Participants transitioned from ISIS 396443-CS4 (NCT02292537)
干预措施: nusinersen (Drug)
Group 3
Participants transitioned from ISIS 396443-CS12 (NCT02052791)
干预措施: nusinersen (Drug)
Group 4
Participants transitioned from ISIS 396443-CS3A (NCT01839656)
干预措施: nusinersen (Drug)
Group 5
Participants transitioned from 232SM202 (NCT02462759)
干预措施: nusinersen (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 up to the end of the study (up to 2848 days)
AE:unfavorable and unintended sign, symptom, or disease temporally associated with study/use of an investigational drug, whether or not it's considered related to investigational drug. SAE:AE that in view of either Investigator/Sponsor, meets any of the following criteria: results in death;is life-threatening:i.e.poses risk of death, hospitalization/it's prolongation;results in a persistent or significant incapacity or substantial disruption of normal life functions;results in congenital anomaly or birth defect in offspring;is an important event in the opinion of Investigator/Sponsor. TEAE: if it was present prior to first dose of nusinersen or first sham procedure in index study and subsequently worsened in severity/was not present prior to first dose of nusinersen or first sham procedure in index study but subsequently appeared.
Number of Participants With Vital Sign Abnormalities Reported as AEs
时间窗: From Day 1 up to the end of the study (up to 2848 days)
The vital sign assessments included blood pressure, temperature, pulse rate, and respiratory rate. Participants with abnormalities in these assessments recorded as AEs were reported.
Number of Participants With Weight Abnormalities Reported as AEs
时间窗: From Day 1 up to the end of the study (up to 2848 days)
Weight decrease was characterized by a decrease of \>=7% from baseline and weight increase was characterized by an increase of \>=7% from baseline. Participants with these abnormalities recorded as AEs were reported.
Number of Participants With Neurological Abnormalities Reported as AEs
时间窗: From Day 1 up to the end of the study (up to 2848 days)
Participants with abnormalities in neurological examinations recorded as AEs were reported.
Number of Participants With Laboratory Abnormalities Reported as AEs
时间窗: From Day 1 up to the end of the study (up to 2848 days)
Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs were reported.
Number of Participants With Coagulation Parameters Reported as AEs
时间窗: From Day 1 up to the end of the study (up to 2848 days)
Coagulation parameters included activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Participants with abnormalities in these coagulation parameters recorded as AEs were reported.
Number of Participants With Clinically Significant Shifts in12 Lead Electrocardiogram (ECG) Results
时间窗: From Day 1 up to the end of the study (up to 2848 days)
Clinical significance of abnormalities in 12 lead ECG was determined based on the investigator's discretion.
Number of Participants Taking Any Concomitant Medication
时间窗: From Day 1 up to the end of the study (up to 2848 days)
A concomitant therapy is any non-protocol-specified drug or substance (including over-the-counter medications, herbal medications, and vitamin supplements) administered between the beginning of screening and the last telephone contact or study visit.
次要结局
- Mean Number of New Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria(MMDR Period: At Day 1800)
- Percentage of CMAP Responders(MMDR Period: At Day 1800)
- Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)(At Day 309)
- Number of Participants Who Died or Met Permanent Ventilation(MMDR Period: Up to Day 1800)
- Number of Participants Not Requiring Permanent Ventilation(MMDR Period: Up to Day 1800)
- Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale(Baseline, Day 2198)
- Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score(MMDR Period: Baseline, MMDR Day 1800)
- Change From Baseline in Revised Upper Limb Module (RULM) Total Score(MMDR Period: Baseline, MMDR Day 1800)
- Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT)(Baseline, Day 2670)
- Number of Participants Who Experienced Contracture Assesment(MMDR Period: At MMDR Day 1800)
- Change From Baseline in Compound Muscular Action Potential (CMAP)(MMDR Period: Baseline, MMDR Day 1800)
- Change From Baseline in Body Length(MMDR Period: up to Day 1800)
- Change From Baseline in Weight(MMDR Period: up to Day 1800)
- Change From Baseline in Weight for Age Percentile(MMDR Period: up to Day 1800)
- Number of Participants Who Achieved Motor Milestones(MMDR Period: up to Day 1800)
- Number of Participants Who Achieved Standing Alone and Walking With Assistance(MMDR Period: up to Day 1800)
- Total Number of Hospitalizations Due to Serious Respiratory Events(Up to day 2520)
- Total Number of Hospitalizations Due to Serious Adverse Events(Up to day 2520)
- Percent of Time in Hospitalization(Upto day 2160)
- Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine by Visit(MMDR Period: Baseline, MMDR Day 1800)
- Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain(MMDR Period: At Day 1800)
- Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) Questionnaire Total Score(MMDR Period: up to Day 1800)
- Number of Participants With Disease-related Hospitalizations and AEs(MMDR Period: up to Day 1800)
- Survival Rate(MMDR Period: up to Day 1800)