An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)
- Registration Number
- NCT01494701
- Lead Sponsor
- Biogen
- Brief Summary
This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Inclusion Criteria
- Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
- Clinical signs attributable to Spinal Muscular Atrophy (SMA)
- 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
- Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
- Presence of a gastric feeding tube
- Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
- Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
- History of brain or spinal cord disease that would interfere with LP procedures or cerebrospinal fluid (CSF) circulation
- Presence of an implanted shunt for the draining of CSF or an implanted Central Nervous System (CNS) catheter
- History of bacterial meningitis
- 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
- Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the participant to undergo study procedures
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 (n=6) nusinersen - Cohort 1 (n=6) nusinersen - Cohort 3 (n=6) nusinersen - Cohort 4 (n=10) nusinersen -
- Primary Outcome Measures
Name Time Method Number of participants that experience Adverse Events (AEs) and Serious Adverse Events Up to 88 Days Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters Up to 88 Days PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible Plasma at 1, 2, 4 and 20 hours after dosing Number of participants with clinically significant physical examination abnormalities Up to 88 Days Number of participants with clinically significant laboratory parameters Up to 88 Days Number of participants with clinically significant vital sign abnormalities Up to 88 Days Number of participants with clinically significant weight abnormalities Up to 88 Days Number of participants with clinically significant electrocardiograms (ECGs) abnormalities Up to 88 Days PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax) Plasma at 1, 2, 4 and 20 hours after dosing PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax) Plasma at 1, 2, 4 and 20 hours after dosing Number of participants with clinically significant neurological examination abnormalities Up to 88 Days Number of participants who use concomitant medications Up to 88 Days PK parameters of nusinersen: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf) Plasma at 1, 2, 4 and 20 hours after dosing
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Children's Hospital Boston
🇺🇸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