Objective: The primary purpose of SMART (NCT04851873), an ongoing, open-label, single-arm, multicenter study, is to systematically collect safety/tolerability data for onasemnogene abeparvovec in symptomatic spinal muscular atrophy (SMA) patients weighing ?8.5 kg to ?21 kg.
Background: Onasemnogene abeparvovec (1.1×10^14 vg/kg) is an approved SMA therapy, with the European label recommending dosing for patients weighing up to 21 kg. Current clinical trial data include patients weighing ?8.5 kg. Additional data for patients ?8.5 kg to ?21 kg are needed to complement emerging real-world use in heavier patients and support informed treatment decisions.
Methods: Approximately 24 participants will be enrolled across three weight groups: ?8.5–13 kg, >13–17 kg, and >17–21 kg. The primary objective is to assess safety/tolerability over 12 months by evaluating treatment-emergent adverse events (AEs) and serious AEs, important identified and potential risks, and changes from baseline for vital signs, cardiac safety, and clinical laboratory assessments. Safety assessments are intended to characterize the known important identified and potential treatment-associated risks with a rigorous safety monitoring regimen. Efficacy will be measured by motor milestone achievement and change from baseline in Hammersmith Functional Motor Scale-Expanded and Revised Upper Limb Module. Key exploratory endpoints include biomarkers, complement biomarkers, actimetry, humoral immunity, vector shedding, pulmonary and bulbar function, and caregiver burden/experience (ACEND PRO tool). Eligibility will be determined in the screening period. Patients will receive prophylactic prednisolone 24 hours before the infusion and for at least 30 days, followed by tapering. On Day 1, participants will receive a single intravenous administration of onasemnogene abeparvovec followed by in-patient safety monitoring for 48 hours. After study completion, participants will be eligible to enroll in a long-term follow-up study.
Results: Study is ongoing.
Conclusions: SMART will expand clinical trial data to SMA patients that weigh up to 21 kg, in alignment with real-world experience.