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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Prospective observational registry
  This prospective observational registry will assess long-term outcomes of patients with a diagnosis of SMA.
• Препарат 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

Первичные конечные точки

• Change in probability of survival of all patients with SMA using Kaplan Meier method to estimate [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline and every 6months through 2 years of follow up, then annually through 15 years of follow up]
• Incidence of treatment emergent adverse events [Срок оценки: Through 15 years of follow up]
• Incidence of treatment emergent serious adverse events [Срок оценки: Through 15 years of follow up]
• Incidence of treatment emergent adverse events related to therapy [Срок оценки: Through 15 years of follow up]
• Incidence of treatment emergent thrombocytopenia, hepatotoxicity and cardiac adverse events [Срок оценки: Through 15 years of follow up]

Вторичные конечные точки (7)

• Change from baseline in rates of hospitalization [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: : 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) [Срок оценки: 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) [Срок оценки: : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up]

Критерии участия

Критерии включения

• 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

Критерии исключения

\- 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Экологическое

Центры проведения

США · 50 центров

• 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
• … и ещё 42 центра

Япония · 19 центров

• 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
• … и ещё 11 центров

South Korea · 7 центров

Список центров уточняется — проверьте первичный протокол.

Португалия · 5 центров

• CHUC - Hospital Pediatrico — Coimbra
• … и ещё 4 центра

Тайвань · 5 центров

Список центров уточняется — проверьте первичный протокол.

Греция · 4 центра

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

Израиль · 4 центра

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

Румыния · 2 центра

Список центров уточняется — проверьте первичный протокол.

Ирландия · 1 центр

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

Польша · 1 центр

• Uniwersytecki Szpital Dzieciec — Lublin

Россия · 1 центр

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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

Идентификаторы

NCT: NCT04174157 · COAV101A12001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗