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

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ClinicalTrials.gov Identifier: NCT04042025
Recruitment Status : Not yet recruiting
First Posted : August 1, 2019
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
AveXis, Inc.

Brief Summary:
This is a long-term follow-up safety and efficacy study of participants in clinical trials for spinal muscular atrophy (SMA) Type 1, Type 2 or Type 3 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 (developmental milestones) 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 Biological: Onasemnogene Abeparvovec-xioi Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : December 31, 2034
Estimated Study Completion Date : December 31, 2034


Arm Intervention/treatment
Cohort 1: Intravenous (IV) Onasemnogene Abeparvovec-xioi
Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi parent study.
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.

Cohort 2: Intrathecal (IT) Onasemnogene Abeparvovec-xioi
Participants received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi parent study.
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.




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 2 years ]
    The HFMSE was devised for use in children with SMA Type 2 and Type 3, 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 24-hour Holter monitor.

  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.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Participants with SMA (with 1, 2 or 3 copies of SMN2) who received onasemnogene abeparvovec-xioi gene replacement therapy in an AveXis 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 ClinicalTrials.gov identifier (NCT number): NCT04042025


Contacts
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Contact: AveXis MedInfo 833-828-3947 medinfo@avexis.com

  Hide Study Locations
Locations
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United States, California
David Geffen School of Medicine at UCLA Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Perry Shieh    310-825-3264    PShieh@mednet.ucla.edu   
Stanford University Medical Center Not yet recruiting
Palo Alto, California, United States, 94304
Contact: John Day    650-725-1442    jwday@stanford.edu   
United States, Colorado
Children's Hospital Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Julie Parsons    720-777-7285    julie.parsons@childrenscolorado.org   
United States, Florida
Nemours Children's Hospital Not yet recruiting
Orlando, Florida, United States, 32827
Contact: Richard Finkel       rfinkel@nemours.org   
United States, Georgia
Center for Rare Neurological Diseases Not yet recruiting
Norcross, Georgia, United States, 30093
Contact: Daniel Tarquinio    617-984-9091    daniel@rareneuro.com   
United States, Illinois
Ann Robert H. Lurie Children's Hospital of Chicago Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Nancy Kuntz    312-227-4000    Nkuntz@luriechildrens.org   
United States, Maryland
John Hopkins Pediatric Neurology, David M. Rubenstein Building Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Tom Crawford    410-955-4259    tcrawfo@jhmi.edu   
United States, Massachusetts
Massachusetts General Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Kathryn Swoboda    617-726-5732    KSWOBODA@mgh.harvard.edu   
Boston Children's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Basil Darras    617-355-8036    basil.darras@childrens.harvard.edu   
United States, Michigan
Spectrum Health System Not yet recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Jena Krueger    616-267-2500    Jena.Krueger@helendevoschildrens.org   
United States, Missouri
Washington Unviersity School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Craig Zaidman    314-362-6981    zaidmanc@neuro.wustl.edu   
United States, New York
Columbia University Not yet recruiting
New York, New York, United States, 10032
Contact: Claudia Chiriboga    212-342-6865    cac3@cumc.columbia.edu   
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27713
Contact: Eddie Smith    919-684-6620    edward.smith@duke.edu   
United States, Ohio
Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Jerry Mendell    614-722-5614    Jerry.Mendell@nationwidechildrens.org   
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Gihan Tennekoon    267-425-0158    tennekoon@email.chop.edu   
Clinic for Special Children Not yet recruiting
Strasburg, Pennsylvania, United States, 17579
Contact: Kevin Strauss    717-687-9407    kstrauss@clinicforspecialchildren.org   
United States, Texas
Children's Med. CTR Ambulatory Care Not yet recruiting
Dallas, Texas, United States, 75207
Contact: Susan Iannaccone    214-456-5220    susan.iannaccone@utsouthwestern.edu   
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84112
Contact: Nicholas Butterfield    801-585-5052    russell.butterfield@hsc.utah.edu   
United States, Virginia
Children's Hospital of The King's Daughters Not yet recruiting
Norfolk, Virginia, United States, 23507
Contact: Crystal Proud    757-668-9920    Crystal.Proud@CHKD.ORG   
Virginia Commonwealth University Not yet recruiting
Richmond, Virginia, United States, 23298
Contact: Nicholas Johnson       Nicholas.Johnson@vcuhealth.org   
United States, Wisconsin
University of Wisconsin, Madison Not yet recruiting
Madison, Wisconsin, United States, 53792
Contact: Meredith Schultz    608-265-1753    mschultz@neurology.wisc.edu   
Australia, New South Wales
Sydney Children's Hospital Westmead Not yet recruiting
Randwick, New South Wales, Australia, 2031
Contact: Michelle Farrar       Michelle.Farrar@health.nsw.gov.au   
Belgium
UZ Gent Not yet recruiting
Gent, Belgium, 9000
Contact: Nicolas Deconick       Nicolas.DECONINCK@huderf.be   
Neuropediatrie-Centre De Reference Des Maladies Not yet recruiting
Liège, Belgium, B-4000
Contact: Aurore Daron       Aurore.daron@chrcitadelle.be   
Canada, Ontario
Children's Hospital of Eastern Ontario Not yet recruiting
Ottawa, Ontario, Canada, K1H8L1
Contact: Hugh McMillan       HMcMillan@cheo.on.ca   
France
Hôpital Armand Trousseau I-Motion - Plateforme d'essais cliniques pédiatriques Not yet recruiting
Paris, France, 75012
Contact: Odile Boespflug-Tanguy       odile.boespflug-tanguy@aphp.fr   
Italy
Instituto Gianninia Gaslini Not yet recruiting
Genova, Italy, 16147
Contact: Claudio Bruno       Claudiobruno@ospedale-gaslini.ge.it   
University of Milan Not yet recruiting
Milan, Italy, 20122
Contact: Stefania Corti       Stefania.Corti@unimi.it   
Carlo Besta Neurological Research Institute Not yet recruiting
Milan, Italy, 20133
Contact: Ricardo Masson       Riccardo.Masson@instituto-besta.it   
Ospedale Pediatrico Bambino Gesù Not yet recruiting
Roma, Italy, 00165
Contact: Enrico Bertini       Bertini@opbg.net   
Fondazione Policlinico Universitario Agostino Gemelli Not yet recruiting
Roma, Italy, 00168
Contact: Eugenio Mercuri       Eugeniomaria.mercuri@policlinicogemelli.it   
Japan
Tokyo Women's Medical University Hospital Not yet recruiting
Tokyo, Japan, 162-0054
Contact: Kayoko Saito       Saito.Kayoko@twmu.ac.jp   
Korea, Republic of
Pusan National University Yangsan Hospital Not yet recruiting
Yangsan, Gyeongsangnam-Do, Korea, Republic of, 50612
Contact: Jin-Hong Shin       Shinzh@gmail.com   
Spain
Hospital Mancha Centro
Alcázar De San Juan, Spain, 13600
Taiwan
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 10048
Contact: Yin-Hsiu Chien       Chienyh@ntu.edu.tw   
United Kingdom
Great Ormond Street Hospital for Children Not yet recruiting
London, United Kingdom, WC1N 3JH
Contact: Francesco Muntoni       F.muntoni@ucl.ac.uk   
Great North Children's Hospital Research Unit Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Contact: Volker Straub       Volker.straub@newcastle.ac.uk   
Sponsors and Collaborators
AveXis, Inc.
Investigators
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Study Chair: Doug Feltner, MD AveXis, Inc.

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Responsible Party: AveXis, Inc.
ClinicalTrials.gov Identifier: NCT04042025     History of Changes
Other Study ID Numbers: AVXS-101-LT-002
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
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 AveXis, Inc.:
Gene replacement

Additional relevant MeSH terms:
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Motor Neuron Disease
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Muscular Atrophies of Childhood
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn