Clinical trial NCT04174157: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Spinal Muscular Atrophy (SMA)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-11-22
Enrollment: 700
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll at least 500 patients with a genetically confirmed diagnosis of SMA. The registry will attempt to enroll all patients treated with OAV-101 in the registry until the end of 2026.

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.

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.

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.

Primary outcomes:
measure: Change in probability of survival of all patients with SMA using Kaplan Meier method to estimate
timeFrame: Based on information collected at Baseline and every 6 months through 2 years of follow-up, then annually through 15 years of follow up.
measure: Change from baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) in infants with pre-symptomatic or type I SMA
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline Hammersmith Infant Neurological Examination (HINE) in infants with pre-symptomatic, type I or type II SMA
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) for patients with type II and III SMA
timeFrame: Baseline and every 6months through 2 years of follow up, then annually through 15 years of follow up
measure: Incidence of treatment emergent adverse events
timeFrame: Through 15 years of follow up
measure: Incidence of treatment emergent serious adverse events
timeFrame: Through 15 years of follow up
measure: Incidence of treatment emergent adverse events related to therapy
timeFrame: Through 15 years of follow up
measure: Incidence of treatment emergent thrombocytopenia, hepatotoxicity and cardiac adverse events
timeFrame: Through 15 years of follow up
Secondary outcomes:
measure: Change from baseline in rates of hospitalization
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline in Zarit Burden Interview
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline in PedsQL Patient interview
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline in PedsQL Parent interview
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: Change from baseline in percent of patients requiring ventilator support (BiPAP, Endotracheal tube)
timeFrame: : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: 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)
timeFrame: Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
measure: 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)
timeFrame: : Baseline and every 6 months through 2 years of follow up, then annually through 15 years of follow up
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles Health
state: California
city: Madera
country: United States
facility: Valley Children's Healthcare
state: California
city: Madera
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Farmington
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Health System
state: Connecticut
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Adventist Health System - Florida
state: Florida
city: Palmetto Bay
country: United States
facility: Jackson South Medical Center
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital (IUHUH)
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health System
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: The State University of New York
state: New York
city: Durham
country: United States
facility: Duke Health
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Memphis
country: United States
facility: Methodist Le Bonheur Healthcare
state: Tennessee
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: Dallas
country: United States
facility: Children's Health
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: CHRISTUS Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Chaïdári
country: Greece
facility: University General Hospital Attikon
state: Athens
city: Penteli
country: Greece
facility: Penteli Children's Hospital
state: Attikis
city: Thessaloniki
country: Greece
facility: St. Sophia Children's Hospital
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki Ippokrateio
city: Dublin
country: Ireland
facility: Children's University Hospital-UCD School of Medicine Scoil an Leighis
city: Be'er Sheva
country: Israel
facility: Soroka Medical Centre
city: Holon
country: Israel
facility: Wolfson Medical Center
city: H̱olon
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Petah tikva
country: Israel
facility: Schneider- Children's Medical Center
city: Nagakute-shi
country: Japan
facility: Aichi Medical University Hospital
state: Aichi
city: Toyoake-shi
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba children's Hospital
state: Chiba
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Gifu-shi
country: Japan
facility: Gifu Prefectural General Medical Center
state: Gifu
city: Sapporo-shi
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Yokohama-shi
country: Japan
facility: Kanagawa Children's Medical Center
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Kumamoto University Hospital
state: Kumamoto
city: Sendai-shi
country: Japan
facility: Miyagi Children's Hospital
state: Miyagi
city: Hokkaido
country: Japan
facility: Obihiro Kosei Hospital
state: Obihiro-shi
city: Moriyama-shi
country: Japan
facility: Shiga Medical Center for Children
state: Shiga
city: Hamamatsu-shi
country: Japan
facility: Hamamatsu University School of Medicine, University Hospital
state: Shizuoka
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo
city: Fukui
country: Japan
facility: Fukui Prefectural Hospital
city: Hokkaido
country: Japan
facility: Nikko Memorial Hospital
city: Saitama
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Children's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Yongin-si
country: Korea, Republic of
facility: Yongin Severance Hospital
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciec
city: Coimbra
country: Portugal
facility: CHUC - Hospital Pediatrico
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitaria de Lisboa Central, EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Porto, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Sao Joao, EPE
city: Bucharest
country: Romania
facility: Centrul de Recuperare pentru Copii dr. Nicolae Robanescu
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Kaohsiung city
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou Branch
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.