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)

Overview

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. The purpose of this registry is to assess the long term outcomes of patients with SMA in the context of advances in treatment options and also to characterize and assess long-term safety and effectiveness of OAV-101.

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.

Interventions

• 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

Primary outcome measures

• 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]
• 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]
• 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]
• 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]

Secondary outcome measures (7)

• 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]
• 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]
• 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]
• 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]

Eligibility criteria

Inclusion criteria

• Patients treated with OAV-101 with a genetically confirmed diagnosis of SMA regardless of the date of diagnosis.
• 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 who are participating in a Compassionate Use Program (CUP) for OAV-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 a genetic or clinical diagnosis of SMA.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Ecologic or community

Study locations

United States · 50 centers

• Phoenix Children's Hospital — Phoenix
• Arkansas Children's Hospital — Little Rock
• Loma Linda University Health — Loma Linda
• Children's Hospital of Los Angeles — Los Angeles
• University of California Los Angeles Health — Los Angeles
• Valley Children's Healthcare — Madera
• Children's Hospital of Orange County — Madera
• University of California Davis Health System — Sacramento
• … and 42 more centers

Japan · 19 centers

• Aichi Medical University Hospital — Nagakute-shi
• Fujita Health University Hospital — Toyoake-shi
• Chiba children's Hospital — Chiba
• Kurume University Hospital — Kurume-shi
• Gifu Prefectural General Medical Center — Gifu
• Sapporo Medical University Hospital — Sapporo
• Kagawa University Hospital — Kita-gun
• Kanagawa Children's Medical Center — Yokohama
• … and 11 more centers

South Korea · 7 centers

Center list to be confirmed — check the primary protocol.

Portugal · 5 centers

• CHUC - Hospital Pediatrico — Coimbra
• … and 4 more centers

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Greece · 4 centers

• University General Hospital Attikon — Chaïdári
• Penteli Children's Hospital — Pentéli
• St. Sophia Children's Hospital — Thessaloniki
• General Hospital of Thessaloniki Ippokrateio — Thessaloniki

Israel · 4 centers

• Soroka Medical Centre — Beersheba
• Wolfson Medical Center — Holon
• Tel-Aviv Sourasky Medical Center — Holon
• Schneider- Children's Medical Center — Petah Tikva

Romania · 2 centers

Center list to be confirmed — check the primary protocol.

Ireland · 1 center

• Children's University Hospital-UCD School of Medicine Scoil an Leighis — Dublin

Poland · 1 center

• Uniwersytecki Szpital Dzieciec — Lublin

Russia · 1 center

Center list to be confirmed — check the primary protocol.

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. PMID 21811307
• Saito K, Benguerba K, Tsuchida K, Yazawa K, Tsumiyama I, Kayama H, Reyna SP, Khan F, Finkel RS. Onasemnogene Abeparvovec in Patients With SMA: Interim Results of the RESTORE Registry in Japan. Ann Clin Transl Neurol. 2026 Jun 9. doi: 10.1002/acn3.70437. Online ahead of print. PMID 42265796
• Erbas Y, Servais L, Shieh PB, Goedeker NL, Waldrop MA, Bo R, Raju D, Benguerba K, Reyna SP, Wolff D, Finkel RS. Trach and treat: Safety and motor outcomes following onasemnogene abeparvovec in patients with spinal muscular atrophy and tracheostomies in the RESTORE registry. J Neuromuscul Dis. 2026 Jul;13(4):788-794. doi: 10.1177/22143602251395173. Epub 2025 Nov 11. PMID 41217888

Identifiers

NCT: NCT04174157 · COAV101A12001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗