Single dose gene replacement therapy clinical trial for infants with genetically diagnosed and pre-symptomatic Spinal Muscular Atrophy

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 44

Inclusion Criteria

All patients:
•Age =6 weeks (=42 days) at time of dose
•Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test
•Compound muscle action potential (CMAP) =2 mV at Baseline
•Gestational age of 35 to 42 weeks
•Genetic diagnosis as described below, obtained from an acceptable newborn or pre-natal screening test method

Patients with 2 copies of SMN2
•Patients with pre-symptomatic SMA Type 1 as determined by the following features:
•Bi-allelic deletion of SMN1
•2 copies of SMN2

Patients with 3 copies of SMN2
•Patients with pre-symptomatic SMA Type 2 as determined by the following features:
•Bi-allelic deletion of SMN1
•3 copies of SMN2

Patients with 4 copies of SMN2
•Patients predominantly with pre-symptomatic SMA Type 3 as determined by the following features:
•Bi-allelic deletion of SMN1
•4 copies of SMN2

Are the trial subjects under 18? yes
Number of subjects for this age range: 44
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Weight at screening visit <2 kg
•Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support) at the screening visit
•Any clinical signs or symptoms at screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA (e.g., tongue fasciculation, hypotonia, areflexia)
•Tracheostomy or current prophylactic use or requirement of non invasive ventilatory support at any time and for any duration prior to screening or during the screening period
•Patients with signs of aspiration/inability to tolerate non thickened liquids based on a formal swallowing test performed as part of screening or patients receiving any non-oral feeding method
•Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation.
•Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
•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 dosing
•Previous, planned or expected major surgical procedure including scoliosis repair surgery/procedure during the study assessment period
•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 4 weeks prior to gene replacement therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab)
•Anti AAV9 antibody titer >1:50 as determined by Enzyme linked Immunosorbent Assay (ELISA) binding immunoassay

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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