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Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04042025
Recruitment Status : Active, not recruiting
First Posted : August 1, 2019
Last Update Posted : February 22, 2024
Information provided by (Responsible Party):
Novartis ( Novartis Gene Therapies )

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.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Type I Spinal Muscular Atrophy Type II Spinal Muscular Atrophy Type III SMA Biological: Onasemnogene Abeparvovec-xioi Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101
Actual Study Start Date : February 10, 2020
Estimated Primary Completion Date : December 31, 2035
Estimated Study Completion Date : December 31, 2035

Arm Intervention/treatment
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.
Biological: 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 β-actin-hybrid promoter. Onasemnogene abeparvovec-xioi administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.
Other Name: Zolgensma

Primary Outcome Measures :
  1. Number of Participants Who Reach Developmental Milestones [ Time Frame: Up to 5 years ]
    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.

  2. Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to 5 years ]
    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.

  3. Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support [ Time Frame: Up to 15 years ]
    Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.

  4. Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support [ Time Frame: Up to 5 years ]
    Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.

  5. Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings [ Time Frame: Up to 5 years ]
    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.

  6. Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements [ Time Frame: Up to 5 years ]
    Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.

  7. Change From Baseline in Height Measurements [ Time Frame: Up to 5 years ]
  8. Change From Baseline in Weight Measurements [ Time Frame: Up to 5 years ]
  9. Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments [ Time Frame: Up to 5 years ]
    Blood samples will be collected for hematology (including complete blood cell count) and chemistry.

  10. Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments [ Time Frame: Up to 5 years ]
    Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.

  11. Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results [ Time Frame: Year 6 to Year 15 ]
    The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.

  12. Number of Participants Who Experience at Least One Serious Adverse Event (SAE) [ Time Frame: Up to 15 years ]

    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

  13. Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI) [ Time Frame: Up to 15 years ]

    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

  14. Change From Baseline in Bayley Scales of Infant and Toddler Development [ Time Frame: Up to 42 months, 15 days of age ]
    Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.

  15. Change From Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to 5 years ]
    RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.

  16. Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older [ Time Frame: Up to 5 years ]
    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)).

  17. Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age [ Time Frame: Up to 5 years ]
    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.

  18. Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) [ Time Frame: Up to 5 years ]
    ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience

  19. Number of Participants With Concomitant Medications Overall and by Type of Medications [ Time Frame: Up to 5 years ]
  20. Number of Participants With Other SMA Therapies Overall and by Type of Medications [ Time Frame: Year 6 to Year 15 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04042025

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Sponsors and Collaborators
Novartis Gene Therapies
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Study Chair: Sitra Tauscher-Wisniewski, MD Novartis Gene Therapies, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Novartis Gene Therapies Identifier: NCT04042025    
Other Study ID Numbers: AVXS-101-LT-002
2019-002611-26 ( EudraCT Number )
205305 ( Other Identifier: JapicCTI )
COAV101A12103 ( Other Identifier: Novartis Pharmaceuticals )
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: February 22, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Gene Therapies ):
Gene replacement
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Muscular Atrophies of Childhood
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn