An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)

An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy

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).

This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc.

In August 2016, sponsorship of the trial was transferred to Biogen.

Key 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.