An Open-Label, Dose Escalation Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Spinal Muscular Atrophy

Study start date: October 31, 2012

Key Inclusion Criteria: Genetic documentation of 5q SMA (homozygous gene deletion or mutation) Clinical signs attributable to SMA Able to complete all study procedures, measurements, and visits and parent/patient 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 medical necessity for invasive or non-invasive ventilation during a 24-hour period Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator Previous scoliosis surgery that would interfere with the lumbar puncture injection procedure Hospitalization for surgery (e.g. 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 at any time during the screening period History of brain or spinal cord disease that would interfere with lumbar puncture procedures or cerebrospinal fluid (CSF) circulation Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system catheter History of bacterial meningitis Dosing with ISIS 396443 in clinical study ISIS 396443-CS1 Cohorts 2, 3, or 4 Dosing with ISIS 396443 in clinical study ISIS 396443-CS10 Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG) at the Screening visit, as assessed by the Site Investigator that would render the subject unsuitable for inclusion Treatment with investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Treatment with valproate or hydroxyurea within 3-months of screening. 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) that would interfere with the assessment of safety or would compromise the ability of the patient to undergo study procedures. NOTE: Other protocol defined inclusion/exclusion criteria may apply.