A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
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|ClinicalTrials.gov Identifier: NCT01839656|
Recruitment Status : Completed
First Posted : April 25, 2013
Results First Posted : October 30, 2018
Last Update Posted : October 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Spinal Muscular Atrophy||Drug: nusinersen||Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Infantile-Onset Spinal Muscular Atrophy|
|Actual Study Start Date :||May 8, 2013|
|Actual Primary Completion Date :||August 21, 2017|
|Actual Study Completion Date :||August 21, 2017|
|Experimental: Nusinersen 6 mg||
Administered by intrathecal (IT) injection
|Experimental: Nusinersen 12 mg||
Administered by intrathecal (IT) injection
- Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit [ Time Frame: Day 1352 or Early Termination ]Section 2 of HINE consists of 8 independent milestone categories. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. Overall, there are a total of 26 milestones that can be achieved across the 8 categories. Improvement was defined as any of the following: 1. An increase from baseline of 2 milestones or more, or the achievement of pincer grasp in the voluntary grasp category 2. An increase from baseline of 2 milestones or more, or achievement of touching toes in the ability to kick category 3. An increase from baseline of 1 milestone or more in any of the remaining 6 categories: head control, rolling, sitting, crawling, standing, or walking.
- Event-free Survival at the End of Study [ Time Frame: Up to Day 1638 ]Event-free survival was defined as the percent of participants who were alive and did not require permanent ventilatory support (defined as tracheostomy or the need for ≥16 hours ventilation/day continuously for at least 2 weeks in the absence of an acute reversible illness) Event-free survival was estimated using Kaplan-Meier methodology.
- Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale [ Time Frame: Day 1352 or Early Termination ]The CHOP-INTEND test includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0 (worst) to 4 (best). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Improvement was defined as an increase in total CHOP INTEND score ≥4 points from baseline as of the last study visit.
- Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude [ Time Frame: Baseline, Day 1072 ]CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A positive change from Baseline indicates that the number of motor neurons increased.
- Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1352 ]AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the subject (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.
- Concentration of Nusinersen in Cerebrospinal Fluid (CSF) [ Time Frame: Day 1135 (Predose) ]The concentration of nusinersen in CSF was measured by using standard laboratory assays.
- PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) [ Time Frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) ]Cmax is the maximum observed concentration of study drug in plasma.
- PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) [ Time Frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) ]Tmax is the time at which Cmax occurs.
- PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) [ Time Frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) ]AUC is area under the plasma concentration-time curve from zero time (Predose) to 4 hours after IT administration of study drug. AUC was determined by using the linear trapezoidal rule.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01839656
|United States, California|
|Stanford University Medical Center|
|Stanford, California, United States, 94305|
|United States, Florida|
|Nemours Children's Hospital|
|Orlando, Florida, United States, 32827|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|The Hospital for Sick Children (SickKids)|
|Toronto, Ontario, Canada, M5G 1X8|
|Study Director:||Medical Director||Biogen|