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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04042025




Registration number
NCT04042025
Ethics application status
Date submitted
31/07/2019
Date registered
1/08/2019
Date last updated
25/04/2025

Titles & IDs
Public title
Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
Scientific title
A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101
Secondary ID [1] 0 0
2019-002611-26
Secondary ID [2] 0 0
AVXS-101-LT-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy Type I 0 0
Spinal Muscular Atrophy Type II 0 0
Spinal Muscular Atrophy Type III 0 0
SMA 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Onasemnogene Abeparvovec-xioi

Other: Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi - Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene.


Treatment: Other: Onasemnogene Abeparvovec-xioi
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 containing the human survival motor neuron gene under the control of the cytomegalovirus enhancer/chicken ß-actin-hybrid promoter. Onasemnogene abeparvovec-xioi administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Reach Developmental Milestones
Assessment method [1] 0 0
Assessed via the developmental milestone checklist, formed of 10 yes/no questions. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone.
Timepoint [1] 0 0
Up to 5 years
Primary outcome [2] 0 0
Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
Assessment method [2] 0 0
The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores on the total scale of 0-66 indicates higher levels of motor ability.
Timepoint [2] 0 0
Up to 5 years
Primary outcome [3] 0 0
Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support
Assessment method [3] 0 0
Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.
Timepoint [3] 0 0
Up to 15 years
Primary outcome [4] 0 0
Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support
Assessment method [4] 0 0
Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.
Timepoint [4] 0 0
Up to 5 years
Primary outcome [5] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings
Assessment method [5] 0 0
The physical examination includes review of the following systems: head, ears, eyes, nose and throat, lungs/thorax, cardiovascular, abdomen, musculoskeletal, neurologic, dermatologic, lymphatic, and genitourinary. In addition, visual inspection of the spine, back, shoulders, and hips looking for spinal curvature and asymmetry will be carried out. Joints will be assessed for loss of mobility and contractures.
Timepoint [5] 0 0
Up to 5 years
Primary outcome [6] 0 0
Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements
Assessment method [6] 0 0
Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.
Timepoint [6] 0 0
Up to 5 years
Primary outcome [7] 0 0
Change From Baseline in Height Measurements
Assessment method [7] 0 0
Timepoint [7] 0 0
Up to 5 years
Primary outcome [8] 0 0
Change From Baseline in Weight Measurements
Assessment method [8] 0 0
Timepoint [8] 0 0
Up to 5 years
Primary outcome [9] 0 0
Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments
Assessment method [9] 0 0
Blood samples will be collected for hematology (including complete blood cell count) and chemistry.
Timepoint [9] 0 0
Up to 5 years
Primary outcome [10] 0 0
Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments
Assessment method [10] 0 0
Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.
Timepoint [10] 0 0
Up to 5 years
Primary outcome [11] 0 0
Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results
Assessment method [11] 0 0
The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.
Timepoint [11] 0 0
Year 6 to Year 15
Primary outcome [12] 0 0
Number of Participants Who Experience at Least One Serious Adverse Event (SAE)
Assessment method [12] 0 0
An SAE is defined as any adverse event (appearance of \[or worsening of any pre existing\]) undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria: * Fatal * Life-threatening * Results in persistent or significant disability/incapacity * Constitutes a congenital abnormality or birth defect * Requires in-patient hospitalization or prolongation of existing hospitalization * Is medically significant e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above
Timepoint [12] 0 0
Up to 15 years
Primary outcome [13] 0 0
Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI)
Assessment method [13] 0 0
An AESI is defined as an AE occurring during any study phase that fulfills one of the following criteria: * Hepatotoxicity * Thrombotic microangiopathy * Cardiac adverse events * Dorsal root ganglia toxicity * New malignancies * New incidence of a neurologic disorder * New incidence of an autoimmune disorder * New incidence of hematologic disorder
Timepoint [13] 0 0
Up to 15 years
Primary outcome [14] 0 0
Change From Baseline in Bayley Scales of Infant and Toddler Development
Assessment method [14] 0 0
Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.
Timepoint [14] 0 0
Up to 42 months, 15 days of age
Primary outcome [15] 0 0
Change From Baseline in Revised Upper Limb Module (RULM) Score
Assessment method [15] 0 0
RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.
Timepoint [15] 0 0
Up to 5 years
Primary outcome [16] 0 0
Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older
Assessment method [16] 0 0
The Cogstate Computerized Cognitive Battery consists of the Identification Test (scored 0 (best) to 1.5708 (worst)), the International Shopping List Test (scored 0 (worst) to 999 (best)), the International Shopping List Test-Delayed Recall (scored 0 (worst) to 999 (best)), the One Card Learning Test (scored 0 (worst) to 1.5708 (best)), and the One Back Test (scored 0 (worst) to 1.5708 (best)).
Timepoint [16] 0 0
Up to 5 years
Primary outcome [17] 0 0
Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age
Assessment method [17] 0 0
The CELF-5 Following Directions and Sentence Repetition subtests use scoring that varies based on age, but will be administered to participants 5-21 years of age. The Following Directions subtest will be scored from 0-33 with higher score being more advanced and the Recalling Sentences subtest will be scored from 0-78 with higher score being more advanced.
Timepoint [17] 0 0
Up to 5 years
Primary outcome [18] 0 0
Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND)
Assessment method [18] 0 0
ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience
Timepoint [18] 0 0
Up to 5 years
Primary outcome [19] 0 0
Number of Participants With Concomitant Medications Overall and by Type of Medications
Assessment method [19] 0 0
Timepoint [19] 0 0
Up to 5 years
Primary outcome [20] 0 0
Number of Participants With Other SMA Therapies Overall and by Type of Medications
Assessment method [20] 0 0
Timepoint [20] 0 0
Year 6 to Year 15

Eligibility
Key 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
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 0 0
2145 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Belgium
State/province [16] 0 0
Gent
Country [17] 0 0
Belgium
State/province [17] 0 0
Liège
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
Italy
State/province [20] 0 0
Genova
Country [21] 0 0
Italy
State/province [21] 0 0
Milan
Country [22] 0 0
Italy
State/province [22] 0 0
Roma
Country [23] 0 0
Japan
State/province [23] 0 0
Tokyo
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taipei
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Gene Therapies
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sitra Tauscher-Wisniewski, MD
Address 0 0
Novartis Gene Therapies, Inc.
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.