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


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Trial ID: NCT03306277


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

Official Title

Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion


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

   - 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

   - 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

   - 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

   - Parent(s)/legal guardian(s) refuses to sign consent form

   - Gestational age at birth < 35 weeks (245 days)


biological: Onasemnogene Abeparvovec-xioi


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Shirley Paulose