Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi

Primary outcomes

1. Number of Participants Who Reach Developmental Milestones

   Time frame: Up to 5 years

   Assessed via the developmental milestone checklist, formed of 10 yes/no questions. 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.

2. Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score

   Time frame: Up to 5 years

   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 rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores on the total scale of 0-66 indicates higher levels of motor ability.

3. Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support

   Time frame: Up to 15 years

   Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.

4. Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support

   Time frame: Up to 5 years

   Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.

5. Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings

   Time frame: Up to 5 years

   The physical examination includes review of the following systems: head, ears, eyes, nose and throat, lungs/thorax, cardiovascular, abdomen, musculoskeletal, neurologic, dermatologic, lymphatic, and genitourinary. In addition, visual inspection of the spine, back, shoulders, and hips looking for spinal curvature and asymmetry will be carried out. Joints will be assessed for loss of mobility and contractures.

6. Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements

   Time frame: Up to 5 years

   Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.

7. Change From Baseline in Height Measurements

   Time frame: Up to 5 years

8. Change From Baseline in Weight Measurements

   Time frame: Up to 5 years

9. Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments

   Time frame: Up to 5 years

   Blood samples will be collected for hematology (including complete blood cell count) and chemistry.

10. Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments

    Time frame: Up to 5 years

    Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.

11. Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results

    Time frame: Year 6 to Year 15

    The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.

12. Number of Participants Who Experience at Least One Serious Adverse Event (SAE)

    Time frame: Up to 15 years

    An SAE is defined as any adverse event (appearance of [or worsening of any pre existing]) undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria:

    • Fatal
    • Life-threatening
    • Results in persistent or significant disability/incapacity
    • Constitutes a congenital abnormality or birth defect
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Is medically significant e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above

13. Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI)

    Time frame: Up to 15 years

    An AESI is defined as an AE occurring during any study phase that fulfills one of the following criteria:

    • Hepatotoxicity
    • Thrombotic microangiopathy
    • Cardiac adverse events
    • Dorsal root ganglia toxicity
    • New malignancies
    • New incidence of a neurologic disorder
    • New incidence of an autoimmune disorder
    • New incidence of hematologic disorder

14. Change From Baseline in Bayley Scales of Infant and Toddler Development

    Time frame: Up to 42 months, 15 days of age

    Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.

15. Change From Baseline in Revised Upper Limb Module (RULM) Score

    Time frame: Up to 5 years

    RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.

16. Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older

    Time frame: Up to 5 years

    The Cogstate Computerized Cognitive Battery consists of the Identification Test (scored 0 (best) to 1.5708 (worst)), the International Shopping List Test (scored 0 (worst) to 999 (best)), the International Shopping List Test-Delayed Recall (scored 0 (worst) to 999 (best)), the One Card Learning Test (scored 0 (worst) to 1.5708 (best)), and the One Back Test (scored 0 (worst) to 1.5708 (best)).

17. Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age

    Time frame: Up to 5 years

    The CELF-5 Following Directions and Sentence Repetition subtests use scoring that varies based on age, but will be administered to participants 5-21 years of age. The Following Directions subtest will be scored from 0-33 with higher score being more advanced and the Recalling Sentences subtest will be scored from 0-78 with higher score being more advanced.

18. Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND)

    Time frame: Up to 5 years

    ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience

19. Number of Participants With Concomitant Medications Overall and by Type of Medications

    Time frame: Up to 5 years

20. Number of Participants With Other SMA Therapies Overall and by Type of Medications

    Time frame: Year 6 to Year 15