Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy.

These were assessed by the investigator.

Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg).

Systolic Blood Pressure-Low:<=5th percentile of the age(Any Age), High:>=90th percentile of the age, gender, and height group (<18 yrs).

Diastolic Blood Pressure-High:>=90th percentile of the age, gender, and height group(<18 yrs).

Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)

Change from baseline in vital signs measurements - Pulse Rate (beats/min

Change from baseline in vital signs measurements - temperature (degrees Celsius)

Temperature-Low:<=35ºC(Any Age),High:>=38.4ºC(<18 yrs).

Change from baseline in vital signs measurements - oxygen saturation level (%).

Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.

The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley scale of Infant and Toddler Development was modified and combined into a single scale expressly for this study, to measure developmental motor milestones. These were assessed via the milestone checklist, formed of 10 yes/no questions with optional video documentation. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.

The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments. Each motor skill item is scored on a 3 point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher level of ability.

The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb preferred by the participant. The total score ranges from 0, if all the items cannot be performed, to 37, if all the activities are achieved fully without any compensation. ' Higher scores indicate higher levels of motor ability.