Intervention: Spinraza
Trial phase: Phase 3
SMILES: COCCOC1C(OP(O)(=S)OCC2OC(n3cnc4c(N)ncnc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(N)nc3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(N)nc3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(N)ncnc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(N)ncnc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(N)ncnc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(=O)[nH]c(N)nc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(N)nc3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cc(C)c(=O)[nH]c3=O)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(=O)[nH]c(N)nc43)C(OCCOC)C2OP(O)(=S)OCC2OC(n3cnc4c(=O)[nH]c(N)nc43)C(OCCOC)C2O)C(COP(O)(=S)OC2C(CO)OC(n3cc(C)c(=O)[nH]c3=O)C2OCCOC)OC1n1cc(C)c(N)nc1=O
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 84
Group description: Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Eligibility criteria:
Key Inclusion Criteria:

Parent or guardian has signed informed consent and, if indicated per participant's age and institutional guidelines, participant has signed informed assent
Be medically diagnosed with Spinal Muscular Atrophy (SMA)
Have onset of clinical signs and symptoms consistent with SMA at greater than 6 months of age
Be able to sit independently, but has never had the ability to walk independently
Have Motor Function Score (Hammersmith Functional Motor Scale - Expanded) greater than or equal to 10 and less than or equal to 54 at Screening
Be able to complete all study procedures, measurements and visits and parent or guardian and subject has adequately supportive psychosocial circumstances, in the opinion of the Investigator
Have an estimated life expectancy of greater than 2 years from Screening, in the opinion of the Investigator
Meet age-appropriate institutional criteria for use of anesthesia and sedation, if use is planned for study procedures
For subjects who have reached reproductive maturity, satisfy study contraceptive requirements

Key Exclusion Criteria:

Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for greater than 6 hours during a 24 hour period, at Screening
Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Site Investigator
Severe contractures or severe scoliosis evident on X-ray examination at Screening
Hospitalization for surgery (i.e., scoliosis surgery, other surgery), pulmonary event, or nutritional support 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, including tumors, or abnormalities by magnetic resonance imaging (MRI) or computed tomography (CT) that would interfere with the LP procedures or cerebrospinal fluid (CSF) circulation
Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter
History of bacterial meningitis
Dosing with IONIS-SMN Rx in any previous clinical study
Prior injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the subject's ability to perform any of the outcome measure testing required in the protocol and from which the subject has not fully recovered or achieved a stable baseline
Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the subject unsuitable for inclusion
Treatment with another investigational drug (e.g., oral albuterol or salbutamol, riluzole, carnitine, creatine, sodium phenylbutyrate, et.c), 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, antisense oligonucleotide therapy, or cell transplantation.
Ongoing medical condition that according to the Site Investigator 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 compromise the ability of the subject to undergo study procedures.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.