Clinical trial NCT04042025: Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
Official title: A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Spinal Muscular Atrophy Type I
Spinal Muscular Atrophy Type II
Spinal Muscular Atrophy Type III
SMA
Keywords: Gene replacement
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-01
Enrollment: 85
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a long-term follow-up safety and efficacy study of participants in clinical trials for spinal muscular atrophy (SMA) who were treated with onasemnogene abeparvovec-xioi. Participants will roll over from their respective previous (parent) study into this long-term study for continuous monitoring of safety as well as monitoring of continued efficacy and durability of response to onasemnogene abeparvovec-xioi treatment.


Eligibility criteria: Inclusion Criteria:

* Any participant with SMA who received onasemnogene abeparvovec-xioi gene replacement therapy in a Novartis Gene Therapies-sponsored clinical study
* Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule

Exclusion Criteria:

* Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study

Primary outcomes:
measure: Number of Participants Who Reach Developmental Milestones
timeFrame: Up to 5 years
measure: Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support
timeFrame: Up to 15 years
measure: Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements
timeFrame: Up to 5 years
measure: Change From Baseline in Height Measurements
timeFrame: Up to 5 years
measure: Change From Baseline in Weight Measurements
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments
timeFrame: Up to 5 years
measure: Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results
timeFrame: Year 6 to Year 15
measure: Number of Participants Who Experience at Least One Serious Adverse Event (SAE)
timeFrame: Up to 15 years
measure: Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI)
timeFrame: Up to 15 years
measure: Change From Baseline in Bayley Scales of Infant and Toddler Development
timeFrame: Up to 42 months, 15 days of age
measure: Change From Baseline in Revised Upper Limb Module (RULM) Score
timeFrame: Up to 5 years
measure: Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older
timeFrame: Up to 5 years
measure: Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age
timeFrame: Up to 5 years
measure: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND)
timeFrame: Up to 5 years
measure: Number of Participants With Concomitant Medications Overall and by Type of Medications
timeFrame: Up to 5 years
measure: Number of Participants With Other SMA Therapies Overall and by Type of Medications
timeFrame: Year 6 to Year 15
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins Hospital - David M. Rubenstein Child Health Building
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals Helen DeVos Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington Unviersity School of Medicine in Saint Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Strasburg
country: United States
facility: Clinic for Special Children
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Health Specialty Center Dallas Campus
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
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
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liège
country: Belgium
facility: Centre de Référence des Maladies Neuromusculaires
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario Research Institute
state: Ontario
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Genova
country: Italy
facility: Instituto Gianninia Gaslini
city: Milan
country: Italy
facility: Universita Degli Studi Di Milano
city: Milan
country: Italy
facility: Istituto Neurologico di Ricerca
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Novartis Gene Therapies, Inc.
name: Sitra Tauscher-Wisniewski, MD
role: STUDY_CHAIR
References:
citation: Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.