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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04174157
Other study ID # AVXS-101-RG-001
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date September 25, 2018
Est. completion date June 30, 2038

Study information

Verified date April 2023
Source AveXis, Inc.
Contact Novartis Gene Therapies (former AveXis) Medinfo
Phone 1-833-828-3947
Email medinfo.gtx@novartis.com
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 500
Est. completion date June 30, 2038
Est. primary completion date June 30, 2038
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility 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.

Study Design


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

Locations

Country Name City State
Greece University General Hospital Attikon Chaïdári Athens
Greece General Hospital of Thessaloniki Ippokrateio Thessaloníki
Ireland Children's University Hospital-UCD School of Medicine Scoil an Leighis Dublin
Israel Soroka Medical Centre Be'er Sheva
Israel Tel-Aviv Sourasky Medical Center H_olon
Israel Wolfson Medical Center Holon
Israel Schneider- Children's Medical Center Petah tikva
Japan Chiba children's Hospital Chiba-shi Chiba
Japan Fukui Prefectural Hospital Fukui
Japan Gifu Prefectural General Medical Center Gifu-shi Gifu
Japan Hamamatsu University School of Medicine, University Hospital Hamamatsu-shi Shizuoka
Japan Obihiro Kosei Hospital Hokkaido Obihiro-shi
Japan Kagawa University Hospital Kita-gun Kagawa
Japan Kumamoto University Hospital Kumamoto-shi Kumamoto
Japan Kurume University Hospital Kurume-shi Fukuoka
Japan Shiga Medical Center for Children Moriyama-shi Shiga
Japan Aichi Medical University Hospital Nagakute-shi Aichi
Japan Sapporo Medical University Hospital Sapporo-shi Hokkaido
Japan Miyagi Children's Hospital Sendai-shi Miyagi
Japan Jichi Medical University Hospital Shimotsuke-shi Tochigi
Japan Center Hospital of the National Center for Global Health and Medicine Shinjuku-ku Tokyo
Japan Tokyo Medical University Hospital Shinjuku-ku Tokyo
Japan Fujita Health University Hospital Toyoake-shi Aichi
Japan Kanagawa Children's Medical Center Yokohama-shi Kanagawa
Korea, Republic of Kyungpook National University Hospital Daegu
Korea, Republic of Seoul National University Bundang Hospital Seongnam-si
Korea, Republic of Severance Hospital Seoul
Korea, Republic of Pusan National University Yangsan Hospital Yangsan
Portugal Centro Hospitalar Universitario Lisboa Norte, EPE Lisboa
Russian Federation Almazov National Medical Research Centre Saint Petersburg
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung city
United States Akron Children's Hospital Akron Ohio
United States Children's Hospital Colorado Aurora Colorado
United States Child Neurology Consultants of Austin Austin Texas
United States University of Virginia Health System Charlottesville Virginia
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States University Hospitals Cleveland Ohio
United States University of Missouri Health System Columbia Missouri
United States Nationwide Children's Hospital Columbus Ohio
United States Children's Health Dallas Texas
United States Duke Health Durham North Carolina
United States Connecticut Children's Medical Center Farmington Connecticut
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Cook Children's Fort Worth Texas
United States Prisma Health Greenville South Carolina
United States Penn State Hershey Hershey Pennsylvania
United States Texas Children's Hospital Houston Texas
United States Indiana University Health University Hospital (IUHUH) Indianapolis Indiana
United States University of Iowa Iowa City Iowa
United States University of Kansas Medical Center Kansas City Kansas
United States Arkansas Children's Hospital Little Rock Arkansas
United States Loma Linda University Health Loma Linda California
United States Children's Hospital of Los Angeles Los Angeles California
United States University of California Los Angeles Health Los Angeles California
United States University of Louisville Louisville Kentucky
United States Children's Hospital of Orange County Madera California
United States Valley Children's Healthcare Madera California
United States University of Wisconsin Madison Wisconsin
United States Methodist Le Bonheur Healthcare Memphis Tennessee
United States Nicklaus Children's Hospital Miami Florida
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States Atlantic Health System Morristown New Jersey
United States Yale-New Haven Health System New Haven Connecticut
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States Oklahoma University Medical Center Oklahoma City Oklahoma
United States Adventist Health System - Florida Orlando Florida
United States Jackson South Medical Center Palmetto Bay Florida
United States Phoenix Children's Hospital Phoenix Arizona
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Oregon Health and Science University Portland Oregon
United States Virginia Commonwealth University Health System Richmond Virginia
United States University of Rochester Medical Center Rochester New York
United States University of California Davis Health System Sacramento California
United States Washington University School of Medicine in St. Louis Saint Louis Missouri
United States University of Utah Salt Lake City Utah
United States CHRISTUS Health San Antonio Texas
United States Rady Children's Hospital San Diego San Diego California
United States Seattle Children's Seattle Washington
United States The State University of New York Stony Brook New York
United States MultiCare Health System Tacoma Washington

Sponsors (2)

Lead Sponsor Collaborator
AveXis, Inc. United BioSource, LLC

Countries where clinical trial is conducted

United States,  Greece,  Ireland,  Israel,  Japan,  Korea, Republic of,  Portugal,  Russian Federation,  Taiwan, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Primary 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
Primary 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
Primary 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
Primary Incidence of treatment emergent adverse events Through 15 years of follow up
Primary Incidence of treatment emergent serious adverse events Through 15 years of follow up
Primary Incidence of treatment emergent adverse events related to therapy Through 15 years of follow up
Primary Incidence of treatment emergent thrombocytopenia, hepatotoxicity and cardiac adverse events Through 15 years of follow up
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
See also
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Recruiting NCT05747261 - Study of the Safety and Efficacy of an Adeno-Associated Viral Vector Carrying the SMN Gene After a Single Intravenous Administration of Escalating Doses in Children With Spinal Muscular Atrophy (BLUEBELL) Phase 1/Phase 2
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Recruiting NCT05335876 - Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials Phase 3
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