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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages Any age
• All sexes
• No healthy volunteers
• Child, Adult, Older adult

Trial locations and contacts

31 sites in 9 countries.

About this study

Official title: A Long-term Follow-up Study of Patients in the Clinical Trials for Spinal Muscular Atrophy Receiving AVXS-101

Conditions

Spinal Muscular Atrophy Type I, Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III, SMA

Being tested

Onasemnogene Abeparvovec-xioi

Keywords

Gene replacement

Medical subject headings

Spinal Muscular Atrophies of Childhood

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Onasemnogene Abeparvovec-xioiBiological

  Also called Zolgensma

  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.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Number of Participants Who Reach Developmental Milestones

   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.

   Measured: Up to 5 years

2. Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score

   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.

   Measured: Up to 5 years

3. Number of Participants Who Experience a Clinically Significant Change From Baseline in Pulmonary Assessment Results and Require Ventilatory Support

   Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.

   Measured: Up to 15 years

4. Number of Participants Who Experience Swallowing Dysfunction and Require Nutritional Support

   Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.

   Measured: Up to 5 years

5. Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examination Findings

   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.

   Measured: Up to 5 years

6. Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Signs Measurements

   Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.

   Measured: Up to 5 years

7. Change From Baseline in Height Measurements

   Measured: Up to 5 years

8. Change From Baseline in Weight Measurements

   Measured: Up to 5 years

9. Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Assessments

   Blood samples will be collected for hematology (including complete blood cell count) and chemistry.

   Measured: Up to 5 years

10. Number of Participants Who Experience a Clinically Significant Change From Baseline in Cardiac Assessments

    Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and Troponin-I.

    Measured: Up to 5 years

11. Number of Participants Who Experience a Clinically Significant Change From Baseline in Observational Phase Questionnaire Results

    The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.

    Measured: Year 6 to Year 15

12. Number of Participants Who Experience at Least One Serious Adverse Event (SAE)

    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

    Measured: Up to 15 years

13. Number of Participants Who Experience at Least One Adverse Event of Special Interest (AESI)

    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

    Measured: Up to 15 years

14. Change From Baseline in Bayley Scales of Infant and Toddler Development

    Third Edition (Bayley-III) to be performed in all patients up to 42 months, 15 days of age.

    Measured: Up to 42 months, 15 days of age

15. Change From Baseline in Revised Upper Limb Module (RULM) Score

    RULM score is based on a scale from 0 to 37 where lower scores reflect poorer upper limb functional ability.

    Measured: Up to 5 years

16. Change From Baseline in Cogstate Computerized Cognitive Battery Performed in Age 48 Months and Older

    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)).

    Measured: Up to 5 years

17. Change From Baseline in Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5) Performed in All Participants 5 to 21 Years of Age

    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.

    Measured: Up to 5 years

18. Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND)

    ACEND score is based on a scale from 1 to 41 where higher scores represent a better caregiver experience

    Measured: Up to 5 years

19. Number of Participants With Concomitant Medications Overall and by Type of Medications

    Measured: Up to 5 years

20. Number of Participants With Other SMA Therapies Overall and by Type of Medications

    Measured: Year 6 to Year 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted1 Aug 2019
2. Study start10 Feb 2020
3. Primary completion31 Dec 2035 (estimated)
4. Study completion31 Dec 2035 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (1)Papers the sponsor has linked to this study.
• Other trials for Spinal Muscular Atrophy Type IStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.