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-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246). The secondary objective is to examine the plasma and cerebrospinal fluid (CSF) pharmacokinetic(s) (PK) of nusinersen administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS2 or ISIS 396443-CS10.
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc. In August 2016, sponsorship of the trial was transferred to Biogen.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Administered by intrathecal (IT) injection
Boston Children's Hospital
Boston, Massachusetts, United States
Columbia University Medical Center
New York, New York, United States
UT Southwestern Medical Center - Children's Medical Center Dallas
Dallas, Texas, United States
University of Utah School of Medicine
Salt Lake City, Utah, United States
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Time frame: Up to 24 Months
Number of participants with clinically significant neurological examination abnormalities
Time frame: Up to 24 Months
Number of participants with clinically significant vital sign abnormalities
Time frame: Up to 24 Months
Number of participants with clinically significant physical examination abnormalities
Time frame: Up to 24 Months
Number of participants with clinically significant weight abnormalities
Time frame: Up to 24 Months
Number of participants with clinically significant laboratory parameters
Time frame: Up to 24 Months
Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters
Time frame: Up to Day 176
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time frame: Up to 24 Months
Change from Baseline in concomitant medications
Time frame: Up to 24 Months
PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax)
Time frame: Pre-dose Day 176, Day 358 and Day 540
PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax)
Time frame: Pre-Dose Day 176, Day 358 and Day 540
PK parameters of nusinersen in CSF levels: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf)
Time frame: Pre-Dose Day 176, Day 358 and Day 540
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