Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Infantile-Onset Spinal Muscular Atrophy
Brief 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.


Options:
A: Key Inclusion Criteria:

* Be born (gestational age) between 37 and 42 weeks
* Be medically diagnosed with spinal muscular atrophy (SMA)
* Have Survival Motor Neuron2 (SMN2) Copy number = 2
* Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
* Be able to follow all study procedures
* Reside within approximately 9 hours ground-travel distance from a participating study center, for the duration of the study

Key Exclusion Criteria:

* Hypoxemia (oxygen \[O2\] saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
* 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 participant unsuitable for participation in the study
* Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study

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

* Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy (SMA) type II or III
* Laboratory documentation of homozygous absence of SMNI exon 7 and/or deletion and mutation on other allele
* MFM relative score (percentage of the maximum sum of both dimensions) \>= 15% (D1 + D2 score)
* HFMS score at baseline \>= 3
* Non ambulant patients defined as patients with HFMS score =\< 38
* Must be 3 years of age or older, but younger than 26 years of age, at time of enrolment
* Age of onset of symptoms =\< 3 years of age
* Signed informed consent of patient and/or parents/guardian
* Laboratory results drawn within 31 days prior to start of study entry demonstrating no clinically significant abnormalities
* Ability to take the study treatment (tested at screening after informed consent)

Exclusion Criteria:

* Evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic pancreatitis, congenital heart defect, known history of metabolic acidosis, hypertension,significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA
* Any clinically significant ECG abnormality
* Any acute co-morbid condition interfering with the well-being of the subject within 7 days of enrolment including bacterial infection, viral infectious processes, food poisoning, temperature \> 37.0 °C, the need for acute treatment or observation due to any other reason, as judged by the investigator; patient can be included after resolution of the acute event
* Use of medications intended for the treatment of SMA including riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, agents anticipated to increase or decrease muscle strength or agents with known or presumed histone deacetylase (HDAC) inhibition, within 30 days prior to study entry. Subjects who use a nebulizer or require an inhaler to steroids will be allowed in the study; however oral use of steroids is prohibited. The oral use of salbutamol is permitted with the following restrictions: patients should have been on salbutamol for at least 6 months before inclusion in the trial, with good tolerance. The dose of salbutamol should remain constant for the duration of the trial. The use of inhaled beta-agonists (for the treatment of asthma crisis for example) is allowed.
* Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment.
* Inability to meet study visit requirements or cooperate reliably with functional testing
* Coexisting medical conditions that contraindicate travel, testing or study medications
* Olesoxime is contraindicated in subjects/patients who develop drug hypersensitivity to it or one of the formulation excipients including hypersensitivity to sesame oil.
* Patients with hemostasis disorders
* Patients with known biliary tract obstruction
* Current or planned pregnancy or nursing period
* For Women: Failure to use one of the following safe methods of contraception:

  1. Female condoms, diaphragm or coil, each used in combination with spermicides
  2. Intra-uterine device
  3. Hormonal contraception in combination with a mechanical method of contraception
* Participation in any other investigational drug or therapy study within the previous 3 months.
C: Inclusion Criteria:

* Patients must have a diagnosis of SMA, confirmed by genetic testing
* Only patients 2 years of age and older at enrollment will be eligible

Exclusion Criteria:

* Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications
* Patients taking medications which may interact with VPA
* Patients on ventilatory support for more than 16 hours per day
* Patients currently enrolled in other treatment trials
D: 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.

Answer: D