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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 : Enrolling by invitation
First Posted : August 1, 2019
Last Update Posted : June 9, 2021
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 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 29, 2035
Estimated Study Completion Date : December 29, 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 with video documentation. 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 indicated higher levels of motor ability.

  3. Number of participants who experience a clinically significant change from baseline in pulmonary assessment results [ 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 [ 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 adverse event (AE) is defined as the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered casually related to the product. An SAE is defined as an AE occurring during any study phase that fulfills one or more of the following criteria:

    • Results in death
    • Is immediately life-threatening
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability or incapacity
    • Results in a congenital abnormality or birth defect
    • Is an important medical event that may jeopardize the patient/subject or may require medical 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:

    • Liver function enzyme elevations 2 × the upper limit of normal
    • New neoplasms or malignancies
    • New incidence or exacerbation of a pre-existing neurologic disorder
    • New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder
    • New incidence of hematologic disorder.

  14. Change from baseline in Bayley Scales of Infant and Toddler Development [ Time Frame: Up to 5 years ]
    Third Edition to be performed during the first 5 years of the study in all patients up to 42 months of age

  15. Change from baseline in Raven's Progressive Matrices (Raven's 2) [ Time Frame: Up to 5 years ]
    to be assessed during the first 5 years of the study in all patients after reaching 42 months of age

  16. Change from baseline in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PediCat) [ Time Frame: Up to 15 years ]
    To be assessed in all patients after reaching 42 months of age and then subsequent Year visits until the End of Study

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 an Novartis Gene Therapies, Inc. 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

Hide Hide 32 study locations
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United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Illinois
Ann Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Maryland
John Hopkins Hospital - David M. Rubenstein Child Health Building
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
Spectrum Health Hospitals Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Washington Unviersity School of Medicine in Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27713
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Clinic for Special Children
Strasburg, Pennsylvania, United States, 17579
United States, Texas
Children's Health Specialty Center Dallas Campus
Dallas, Texas, United States, 75235
United States, Utah
University of Utah Health
Salt Lake City, Utah, United States, 84112
United States, Virginia
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Wisconsin
University of Wisconsin, Madison
Madison, Wisconsin, United States, 53792
Australia, New South Wales
Sydney Children's Hospital
Randwick, New South Wales, Australia, 2145
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Centre de Référence des Maladies Neuromusculaires
Liège, Belgium, B-4000
Canada, Ontario
Children's Hospital of Eastern Ontario Research Institute
Ottawa, Ontario, Canada, K1H8L1
Hôpital Armand Trousseau
Paris, France, 75012
Instituto Gianninia Gaslini
Genova, Italy, 16147
Universita Degli Studi Di Milano
Milan, Italy, 20122
Istituto Neurologico di Ricerca
Milan, Italy, 20133
Fondazione Policlinico Universitario Agostino Gemelli
Roma, Italy, 00168
Tokyo Women's Medical University Hospital
Tokyo, Japan, 162-8666
National Taiwan University Hospital
Taipei, Taiwan, 10048
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom, WC1N 3JH
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Novartis Gene Therapies
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Study Chair: Sitra Tauscher-Wisniewski, MD Novartis Gene Therapies, Inc.
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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 )
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 2021
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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Motor Neuron Disease
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
Neurodegenerative Diseases
Neuromuscular Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn