Health Condition 1: G121- Other inherited spinal muscular atrophy
Conditions
Interventions
Intervention1: OAV101: Single intrathecal dose of 1.2 x 1014 vector genomes
Control Intervention1: Sham Procedure: It consists of a small needle prick on the lower back at the location where the lumb
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: - Diagnostic confirmation during screening period of SMA caused by biallelic SMN1 pathogenic variants affecting SMN1 and 2-4 copies of SMN2 - The patient must be treatment naive for all SMN dependent therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)). - = 2 years and - Onset of clinical signs and symptoms at = 6 months of age - Patient must have a complete HFMSE assessment, with available total score as administered by qualified clinical evaluator during the screening period for trial eligibility - Able to sit independently at screening, but has never had the ability to walk independently. --Definition of sitting independently: Child sits up straight with the head erect for at least 10 seconds without using arms or hands to balance body or support position (Wijnhoven et al 2004). --Definition of walking independently: The child is able to balance the body and control forward stepping movements without assistance (Wijnhoven et al 2004).
Exclusion criteria
Exclusion criteria: - Anti-adeno-associated virus serotype 9 (AAV9) antibody titers > 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) binding immunoassay. NOTE: A negative anti-AAV9 antibody titer is defined as = 1:50. - Presence of the following: . An active infectious process requiring systemic antiviral or antimicrobial therapy at any time between onset of screening and dosing of OAV101 or the sham procedure · An active but untreated viral or bacterial infectious process at any time between onset of screening and dosing of OAV101 or the sham procedure · Any febrile illness within two weeks prior to start of screening, during screening period or during baseline period up to OAV101 treatment or sham procedure · Hepatic dysfunction (i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH), > upper limit of normal (ULN) (Common Terminology Criteria for Adverse Events (CTCAE) grade1 or greater) at Screening Visit 1. NOTE: In the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary · Requiring invasive or awake noninvasive ventilation for > 6 hours during a 24-hour period, invasive or noninvasive ventilation for > 12 hours during a 24-hour period, or requiring tracheostomy during the 4 weeks prior to screening or baseline. · Complications at screening, as determined by theInvestigator, that would interfere with motor efficacy assessments . Body mass index (BMI) < 3rd percentile
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the = 2 to 18 years age groupTimepoint: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| . Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the = 2 to 5 years age group • Change from baseline in RULM at the end of Follow-up Period 1 in treated patients compared to sham controls in the = 2 to 18 years age group • Change from baseline in the RULM at the end of Follow-up Period 1 in treated patients compared to sham controls in the = 2 to 5 years age groupTimepoint: Week 52 | — |
Countries
Brazil, China, Colombia, Denmark, Egypt, India, Malaysia, Mexico, Russian Federation, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, United States of America, Viet Nam
Contacts
Public ContactMurugananthan K
Novartis Healthcare Private Limited
Outcome results
None listed