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

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 27

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 27
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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