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

• ClinicalTrials.gov Identifier: NCT04174157
• Recruitment Status: Recruiting
• First Posted: November 22, 2019
• Last Update Posted: April 19, 2023
• Sponsor: AveXis, Inc.
• Collaborator: United BioSource, LLC
• Information provided by (Responsible Party): AveXis, Inc.

Tracking Information

• First Submitted Date: September 12, 2019
• First Posted Date: November 22, 2019
• Last Update Posted Date: April 19, 2023
• Actual Study Start Date: September 25, 2018
• Estimated Primary Completion Date: June 30, 2038 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2019)

• Change from baseline in rates of hospitalization [ Time Frame: 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 [ Time Frame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up ]
  Zarit Burden Total Score ranges from 0 to 88. A higher score correlates with higher level of burden.
• Change from baseline in PedsQL Patient interview [ Time Frame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up ]
  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
• Change from baseline in PedsQL Parent interview [ Time Frame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up ]
  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
• Change from baseline in percent of patients requiring ventilator support (BiPAP, Endotracheal tube) [ Time Frame: : 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) [ Time Frame: 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) [ Time Frame: : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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: 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.
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Ecologic or Community; Time Perspective: Prospective
• Target Follow-Up Duration: 15 Years
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The study will enroll at least 500 patients with a diagnosis of SMA. The registry will attempt to enroll all patients treated with AVXS-101 in the registry during 5 years of recruitment.
• Condition: Spinal Muscular Atrophy (SMA)

Intervention

• Other: Prospective observational registry
  This prospective observational registry will assess long-term outcomes of patients with a diagnosis of SMA.
• Drug: Zolgensma
  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

Study Groups/Cohorts

Prospective observational registry

This is a prospective, multi center, multinational, non-interventional observational registry.

Interventions:

• Other: Prospective observational registry
• Drug: Zolgensma

• Publications *: Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, Flynn K, Hendrickson BC, Scholl T, Sirko-Osadsa DA, Allitto BA. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012 Jan;20(1):27-32. doi: 10.1038/ejhg.2011.134. Epub 2011 Aug 3.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 20, 2019): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2038
• Estimated Primary Completion Date: June 30, 2038 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Gene Therapies (former AveXis) Medinfo; 1-833-828-3947; medinfo.gtx@novartis.com

• Listed Location Countries: Greece, Ireland, Israel, Japan, Korea, Republic of, Portugal, Russian Federation, Taiwan, United States

Administrative Information

• NCT Number: NCT04174157
• Other Study ID Numbers: AVXS-101-RG-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

Plan Description

Authorship of planned manuscripts for submission to medical journals shall be determined in accordance with the International Committee of Medical Journal Editors (ICMJE) Uniform Requirements for Manuscripts Submitted to Biomedical Journals (www.icmje.org).

The physician agrees that if the physician is part of a multi-center registry, the physician shall coordinate in advance any intended disclosure of the results of the registry with Novartis Gene Therapies to ensure that the results of individual physicians are not published or presented before those of the multi-center registry, unless otherwise agreed to in writing by Novartis Gene Therapies.

• Current Responsible Party: AveXis, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: AveXis, Inc.
• Original Study Sponsor: Same as current
• Collaborators: United BioSource, LLC

Investigators

• Study Director: Eric Faulkner; Novartis Gene Therapies

• PRS Account: AveXis, Inc.
• Verification Date: April 2023