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

Study Overview
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Brief Summary
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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.

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

Conditions
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SMA, Spinal Muscular Atrophy Type I, Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III

Intervention / Treatment
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* Biological: Onasemnogene Abeparvovec-xioi


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any participant with SMA who received onasemnogene abeparvovec-xioi gene replacement therapy in a Novartis Gene Therapies-sponsored clinical study Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule Exclusion Criteria: Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi<br>Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene. | Biological: Onasemnogene Abeparvovec-xioi<br>* Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 containing the human survival motor neuron gene under the control of the cytomegalovirus enhancer/chicken β-actin-hybrid promoter. Onasemnogene abeparvovec-xioi administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.<br>* Other names: Zolgensma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Reach Developmental Milestones | 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. | Up to 5 years | 
| Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score | 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. | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support | Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support. | Up to 15 years | 
| Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support | Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question. | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings | 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. | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements | Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry. | Up to 5 years | 
| Change From Baseline in Height Measurements |  | Up to 5 years | 
| Change From Baseline in Weight Measurements |  | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments | Blood samples will be collected for hematology (including complete blood cell count) and chemistry. | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments | Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I. | Up to 5 years | 
| Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results | The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support. | Year 6 to Year 15 | 
| Number of Participants Who Experience at Least One Serious Adverse Event (SAE) | 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 | Up to 15 years | 
| Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI) | 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 | Up to 15 years | 
| Change From Baseline in Bayley Scales of Infant and Toddler Development | Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age. | Up to 42 months, 15 days of age | 
| Change From Baseline in Revised Upper Limb Module (RULM) Score | RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability. | Up to 5 years | 
| Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older | 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)). | Up to 5 years | 
| Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age | 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. | Up to 5 years | 
| Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) | ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience | Up to 5 years | 
| Number of Participants With Concomitant Medications Overall and by Type of Medications |  | Up to 5 years | 
| Number of Participants With Other SMA Therapies Overall and by Type of Medications |  | Year 6 to Year 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene replacement