Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Delivering AVXS-101
Brief Summary: The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of AVXS-101 as a treatment of spinal muscular atrophy Type 1 (SMN1).


Options:
A: Inclusion Criteria:

* Six or nine months of age and younger (depending on cohort) on day of vector infusion with Type 1 SMA as defined by the following features:

  * Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
  * Onset of disease at birth up to 6 months of age.
  * Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.

Exclusion Criteria:

* Active viral infection (includes HIV or serology positive for hepatitis B or C)
* Use of invasive ventilatory support (tracheotomy with positive pressure)\* or pulse oximetry \<95% saturation.
* Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
* Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
* Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
* Patients with Anti-AAV9 antibody titers \>1:50 as determined by ELISA binding immunoassay.
* Abnormal laboratory values considered clinically significant (GGT \> 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb \< 8 or \> 18 g/Dl; WBC \> 20,000 per cmm) Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
* Family does not want to disclose patient's study participation with primary care physician and other medical providers.
* Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
* Patients with a single base substitution in SMN2 (c.859G\>C in exon 7) will be excluded based on predicted mild phenotype.
B: 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.
C: 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.
D: Inclusion Criteria:

* Regularly attended at the Out-patient Service of Neuromuscular Disorders and Child Neurology of our Institution;
* More than 2 years olf and had a molecular analysis of Spinal Muscular Atrophy;

Exclusion Criteria:

* Had been submitted into a surgery recently;
* Did not come to the evaluation and medical sessions:
* Did not take the medication correctly

Answer: A