A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
Condition: Spinal Muscular Atrophy
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy
Intervention: nusinersen
Intervention description: Administered by intrathecal (IT) injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 21 Days
Maximum age: 210 Days
Healthy volunteers: No
Keywords: Spinal Muscular Atrophy; SMA; SMN; SMNRx; ISIS-SMNRx; ISIS 396443; IONIS-SMNRx; Spinraza; Nusinersen

Summary:

      The primary objective is to examine the clinical efficacy of multiple doses of nusinersen
      (ISIS 396443) administered intrathecally to participants with Infantile-Onset Spinal Muscular
      Atrophy (SMA). The secondary objectives are to examine the safety and tolerability of
      multiple doses of nusinersen administered intrathecally to participants with infantile-onset
      SMA and to examine the cerebral spinal fluid (CSF) and plasma Pharmacokinetics (PK) of
      multiple doses of nusinersen administered intrathecally to participants with infantile-onset
      SMA.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Genetic documentation of 5q SMA (homozygous gene deletion or mutation)

          -  Onset of clinical signs and symptoms consistent with SMA at ≥ 21 days and <6 months
             (180 days) of age

          -  At study entry, receiving adequate nutrition and hydration (with or without
             gastrostomy), in the opinion of the Site Investigator

          -  Body weight >5th percentile for age using Center of Disease Control and Prevention
             (CDC) guidelines

          -  Medical care meets and is expected to continue to meet guidelines set out in the
             Consensus Statement for Standard of Care in SMA (Wang et al. 2007), in the opinion of
             the Site Investigator

          -  Gestational age of 35 to 42 weeks and gestation body weight ≥2 kg

          -  Reside within approximately 9 hours ground-travel distance from a participating study
             center for the duration of the study. Residence >2 hours ground-travel distance from a
             study center must obtain clearance from the Site Investigator and the study Medical
             Monitor

          -  Able to complete all study procedures, measurements and visits and parent or
             guardian/participant has adequately supportive psychosocial circumstances, in the
             opinion of the Site Investigator

        Exclusion Criteria:

          -  Hypoxemia (O2 saturation awake <96% or O2 saturation asleep <96%, without ventilation
             support)

          -  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 the lumbar puncture
             (LP) procedures, CSF circulation, or safety assessments

          -  Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an
             implanted central nervous system (CNS) catheter

          -  History of bacterial meningitis

          -  Clinically significant abnormalities in hematology or clinical chemistry parameters,
             as assessed by the Site Investigator, at screening that would render the participant
             unsuitable for inclusion

          -  Treatment with another investigational drug (e.g., albuterol, riluzole, carnitine,
             creatine, sodium phenylbutyrate, salbutamol, valproate, hydroxyurea etc), biological
             agent, or device within 90 days prior to enrollment or anytime during the study. Any
             history of gene therapy or cell transplantation

          -  The participants parent(s) or legal guardian(s) is unable to understand the nature,
             scope, and possible consequences of the study, or does not agree to comply with the
             protocol defined schedule of assessments

          -  Ongoing medical condition that according to the Site Investigator would interfere with
             the conduct and assessments of the study. Examples are medical disability other than
             SMA that would interfere with the assessment of safety or would compromise the ability
             of the participant to undergo study procedures

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.