Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials

Study Overview
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Brief Summary
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This is a global, prospective, multi-center study that is designed to assess the long-term safety and efficacy of OAV101 in patients who participated in an OAV101 clinical trial. The assessments of safety and efficacy in Study COAV101A12308 will continue for 15 years from the date of OAV101 administration in the parent study.

Detailed Description
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The study is comprised of a Baseline Period and 3 Follow-up Periods. Follow-up Periods 1 and 2 consist of in-person visits and Period 3 consists of tele-visits. Follow-up Periods 1 and 2, which includes Baseline through Year 5 visits, assessments will be performed at the Investigational site. During Follow-up Period 3 (Year 6 to up to Year 15 after OAV101 administration), participants/caregivers will be contacted using tele-visits annually for remote assessments. All patients will enter the study at the baseline visit and continue until 15 years since OAV101 administration is reached. Total duration of participation in the study will be dependent upon time of enrollment relative to OAV101 administration and will vary by participant.

Official Title
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Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 IT or OAV101 IV in Clinical Trials

Conditions
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Spinal Muscular Atrophy (SMA)

Intervention / Treatment
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* Biological: onasemnogene abeparvovec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participated in an OAV101 clinical trial. Written informed consent must be obtained before any assessment is performed. Patient/Parent/legal guardian willing and able to comply with study procedures. Exclusion Criteria: There are no exclusion criteria for this 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 |
| --- | --- |
| Experimental: Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec<br>Patients who received OAV101 IT or OAV101 IV in AveXis/ Novartis or Novartis Gene Therapies Phase I to IIIb clinical trials | Biological: onasemnogene abeparvovec<br>* Onasemnogene abeparvovec is a non-replicating recombinant adeno-associated virus serotype 9 containing the human survival motor neuron gene under the control of the ytomegalovirus enhancer/chicken β-actin-hybrid promoter. Onasemnogene abeparvovec is 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 with treatment-emergent serious adverse events (SAEs) | 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 anomaly/birth defect, fetal death or congenital abnormality or birth defect requires in-patient hospitalization or prolongation of existing hospitalization, unless hospitalization is for routine treatment or monitoring of the studied indication, not associated with any deterioration in condition 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 with important identified and important potential risks (Adverse Events of Special Interest (AESI)) | The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator. | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist | The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone. | 5 years | 
| The number of participants demonstrating maintenance of each developmental milestone according to the Developmental Milestone Checklist | The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone. | 5 years | 
| Change from Baseline in the Hammersmith Functional Motor Scale - Expanded (HFMSE) total score | The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability. | 5 years | 
| Change from Baseline in the Revised Upper Limb Module (RULM) total score | The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength, Spinal Muscular Atrophy (SMA), survival motor neuron 1 gene (SMN1), SMN protein depletion, survival motor neuron 2 gene (SMN2), chromosome 5q13, neurogenetic disorder, onasemnogene abeparvovec