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Phase 3 pivotal US trial studying open-label intravenous administration of onasemnogene abeparvovec-xioi in spinal muscular atrophy (SMA) Type 1 participants.


SMA - Spinal Muscular Atrophy, Gene Therapy

Recruitment Status


Detailed Description

Phase 3, open-label, single-arm, single-dose, study of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by nonfunctional survival motor neuron 1 gene (SMN1) with 1 or 2 copies of survival motor neuron 2 gene (SMN2). Fifteen (15) participants < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

Eligibility Criteria

Inclusion Criteria:

Participants with SMA Type 1 as determined by the following features: a. Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 1 or 2 copies of SMN2 (inclusive of the known SMN2 gene modifier mutation (c.859G>C))2
The first 3 participants enrolled must meet the criteria for the Intent-To-Treat Population
Participants must be < 6 months (< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
Participants must have a swallowing evaluation test performed prior to administration of gene replacement therapy
Up-to-date on childhood vaccinations. Seasonal vaccinations that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics
Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedule

Exclusion Criteria:

Previous, planned or expected scoliosis repair surgery/procedure during the study assessment period
Pulse oximetry < 96% saturation at screening while the participant is awake or asleep without any supplemental oxygen or respiratory support, or for altitudes > 1000 m, oxygen saturation < 92% awake or asleep without any supplemental oxygen or respiratory support Pulse oximetry saturation may decrease to < 96% after screening provided that the saturation does not decrease by ≥ 4 percentage points
Tracheostomy or current use or requirement of non-invasive ventilatory support averaging ≥ 6 hours daily over the 7 days prior to the screening visit; or ≥ 6 hours/day on average during the screening period or requiring ventilatory support while awake over the 7 days prior to screening or at any point during the screening period prior to dosing
Participants with signs of aspiration/inability to tolerate non-thickened- liquids based on a formal swallowing test performed as part of screening. Participants with a gastrostomy tube who pass the swallowing test will be allowed to enroll in the study
Participants whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
Active viral infection (includes human immunodeficiency virus [HIV] or positive serology for hepatitis B or C, or Zika virus)
Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening
Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to screening
Severe non-pulmonary/respiratory tract infection within 4 weeks before administration of gene replacement therapy or concomitant illness that creates unnecessary risks for gene replacement therapy such as: a. Major renal or hepatic impairment b. Known seizure disorder c. Diabetes mellitus d. Idiopathic hypocalcuria e. Symptomatic cardiomyopathy
Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 3 months prior to gene replacement therapy
Anti-adeno-associated virus serotype 9 (AAV9) antibody titer > 1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential participant demonstrate Anti-AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the Anti-AAV9 antibody titer upon retesting is ≤ 1:50
Clinically significant abnormal laboratory values (gamma glutamyl- transpeptidase [GGT], ALT, and AST > 3 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy
Participation in recent SMA treatment clinical study (with the exception of observational Cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product, or therapy administered with the intent to treat SMA at any time prior to screening for this study. Oral β-agonists must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
Expectation of major surgical procedures during the study assessment period
Parent(s)/legal guardian(s) unable or unwilling to comply with study procedures or inability to travel for repeat visits
Parent(s)/legal guardian(s) unwilling to keep study results/observations confidential or to refrain from posting confidential study results/observations on social media sites
Parent(s)/legal guardian(s) refuses to sign consent form
Gestational age at birth < 35 weeks (245 days)


Intervention Type

Intervention Name


Onasemnogene Abeparvovec-xioi


Phase 3



Min Age


Max Age

180 Days

Download Date

August 16, 2022

Principal Investigator


Primary Contact Information

For more information on this trial, visit


For more information and to contact the study team:

Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1 NCT03306277