This is a long-term follow-up safety and efficacy study of participants in clinical
trials for spinal muscular atrophy (SMA) who were treated with onasemnogene
abeparvovec-xioi. Participants will roll over from their respective previous (parent)
study into this long-term study for continuous monitoring of safety as well as monitoring
of continued efficacy and durability of response to onasemnogene abeparvovec-xioi
treatment.

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

Spinal Muscular Atrophy Type I

Spinal Muscular Atrophy Type II

Spinal Muscular Atrophy Type III

Onasemnogene Abeparvovec-xioi

A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101

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.

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.

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

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

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.

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

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

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

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

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

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

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

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

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)).

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.

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

Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene
abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an
onasemnogene.

Stanford University Medical Center

Children's Hospital Colorado

Ann Robert H. Lurie Children's Hospital of Chicago

John Hopkins Hospital - David M. Rubenstein Child Health Building

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

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status