Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)

Study Overview
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Brief Summary
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Spinal muscular atrophy (SMA) is a neurogenetic disorder caused by a loss or mutation in the survival motor neuron 1 gene (SMN1) on chromosome 5q13, which leads to reduced SMN protein levels and a selective dysfunction of motor neurons. SMA is an autosomal recessive, early childhood disease with an incidence of 1:10,000 live births. SMA is the leading cause of infant mortality due to genetic diseases. Until recently, the mainstay of treatment for these patients was supportive medical care. However, advances in medical treatment focusing on gene replacement, gene enhancement, motor neuron protection and muscle enhancement is likely to change the management and prognosis of these patients in the future. The purpose of this registry is to assess the long term outcomes of patients with SMA in the context of advances in treatment options.

Detailed Description
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This is a prospective, multi center, multinational, non-interventional observational study. All patients will be managed according to the clinical site's normal clinical practice, i.e., the diagnostic and clinical treatment/practice process that a clinician chooses according to their clinical judgement for an SMA patient. Clinical care will not be driven by the protocol. No additional visits or investigations will be performed beyond normal clinical practice. Patients will be followed for 15 years from enrolment or until death, whichever is sooner.

Official Title
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A Prospective, Long-Term Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)

Conditions
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Spinal Muscular Atrophy (SMA)

Intervention / Treatment
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* Other: Prospective observational registry
* Drug: Zolgensma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with SMA, genetically confirmed on or after 24 May 2018. Appropriate consent/assent has been obtained for participation in the registry Exclusion Criteria: - Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat SMA. Note: Patients that are participating in a Compassionate Use Program (CUP) for AVXS-101 (Zolgensma) such as a Managed Access Program (MAP), an Expanded Access Program (EAP), Single Patient Investigational New Drug (IND) (SPI) or Named Patient Program (NPP) are eligible to enroll in the registry regardless of the date of genetic confirmation of SMA.
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective observational registry<br>This is a prospective, multi center, multinational, non-interventional observational registry. | Other: Prospective observational registry<br>* This prospective observational registry will assess long-term outcomes of patients with a diagnosis of SMA.<br>Drug: Zolgensma<br>* Zolgensma will be given to patients as per normal clinical practice and clinical care will not be mandated by the protocol. As such, the decision to prescribe Zolgensma is separate from the decision to include the patient in this study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in probability of survival of all patients with SMA using Kaplan Meier method to estimate |  | Based on information collected at Baseline and every 6 months through 2 years of follow-up, then annually through 15 years of follow up. | 
| Change from baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) in infants with pre-symptomatic or type I SMA | CHOP INTEND score ranges from 0 to 64 with higher scores indicating higher motor function | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline Hammersmith Infant Neurological Examination (HINE) in infants with pre-symptomatic, type I or type II SMA | HINE score range from 0 to 26 with higher scores indicating more development. | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) for patients with type II and III SMA | HFMSE score range from 0 to 66 with the higher scores indicating more development. | Baseline and every 6months through 2 years of follow up, then annually through 15 years of follow up | 
| Incidence of treatment emergent adverse events |  | Through 15 years of follow up | 
| Incidence of treatment emergent serious adverse events |  | Through 15 years of follow up | 
| Incidence of treatment emergent adverse events related to therapy |  | Through 15 years of follow up | 
| Incidence of treatment emergent thrombocytopenia, hepatotoxicity and cardiac adverse events |  | Through 15 years of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in rates of hospitalization |  | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in Zarit Burden Interview | Zarit Burden Total Score ranges from 0 to 88. A higher score correlates with higher level of burden. | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in PedsQL Patient interview | PedsQL Total Scale Score is average of all items and ranges from 0 to 100. A higher score correlates with better Health-Related Quality of Life | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in PedsQL Parent interview | PedsQL Total Scale Score is average of all items and ranges from 0 to 100. A higher score correlates with better Health-Related Quality of Life | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in percent of patients requiring ventilator support (BiPAP, Endotracheal tube) |  | : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in in percent of patients requiring nutritional support (Gastrostomy Tube, Gastrojejunal tube (GT) with Nissen fundoplication, GT without Nissen fundoplication, Nasogastrictube, Nasojejunaltube or Percutaneous endoscopic gastrostomy) |  | Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up | 
| Change from baseline in in percent of patients requiring mobility device support (Ankle-Foot Orthoses, Supramalleolar Orthosis, Orthotic/shoe inserts, Knee immobilizers, Knee-Ankle-Foot Orthoses , Hand splints, Spinal bracing) |  | : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up |