Spinal Muscular Atrophy
Conditions
Keywords
Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443, IONIS-SMNRx, IONIS-SMN Rx, Spinraza
Brief summary
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.
Detailed description
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc. In August 2016, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGnusinersen
Administered by intrathecal (IT) injection
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical signs attributable to Spinal Muscular Atrophy * Satisfactory completion of dosing and all study visits in ISIS 396443-CS2 (NCT01703988) or ISIS 396443 CS10 (NCT01780246) 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 Key
Exclusion criteria
* Have any new or worsening of existing condition which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with the participant participating in or completing the study. * Dosing in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246) within 180 days (6 months) of screening, or longer ago than 396 days (13 months) from screening * 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 * Clinically significant abnormalities in hematology or clinical chemistry parameters * Treatment with another investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Any history of gene therapy or cell transplantation. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in concomitant medications | Up to 24 Months |
| Number of participants with clinically significant laboratory parameters | Up to 24 Months |
| Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters | Up to Day 176 |
| Number of participants with clinically significant electrocardiograms (ECGs) abnormalities | Up to 24 Months |
| Number of participants that experience Adverse Events (AEs) and Serious Adverse Events | Up to 24 Months |
| Number of participants with clinically significant neurological examination abnormalities | Up to 24 Months |
| Number of participants with clinically significant vital sign abnormalities | Up to 24 Months |
| Number of participants with clinically significant physical examination abnormalities | Up to 24 Months |
| Number of participants with clinically significant weight abnormalities | Up to 24 Months |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax) | 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) | Pre-Dose Day 176, Day 358 and Day 540 |
| PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax) | Pre-dose Day 176, Day 358 and Day 540 |
Countries
United States
Outcome results
None listed