Abstract Details

Title Design and Rationale of SMART, a Phase IIIb Study Evaluating Intravenous Onasemnogene Abeparvovec in Spinal Muscular Atrophy

Topic Child Neurology and Developmental Neurology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-003

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 (1.1×10¹⁴ 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.

Design/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.

Authors/Disclosures
Sandra P. Reyna, MD PRESENTER	Dr. Reyna has received personal compensation for serving as an employee of Novartis Gene Therapies.
Arseniy Lavrov (Novartis)	Dr. Lavrov has received personal compensation for serving as an employee of Novartis. Dr. Lavrov has stock in Novartis.
	No disclosure on file
	No disclosure on file

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