Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

A Phase IIIb, Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Gene Replacement Therapy With Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.

This was an open-label, single arm, multi-center study designed to evaluate the safety, tolerability and efficacy of OAV101 in participants with SMA who weigh ≥ 8.5 kg and ≤ 21 kg. The study aimed to enroll approximately 24 to 30 participants, with approximately 6 to 10 participants across each of 3 weight brackets (8.5 to 13 kg, >13 to 17 kg, >17 to 21 kg).

Eligible participants received a single administration of OAV101 at the approved dose of 1.1e14 vg/kg on Day 1 (Treatment period), and were followed for a period of 12 months.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101 on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.

After study completion, eligible participants could enroll into a Long Term follow-up study to collect additional safety and efficacy data. (COAV101A12308 (NCT05335876) https://classic.clinicaltrials.gov/ct2/show/NCT05335876?term=COAV101A12308\&draw=2\&rank=1))

Inclusion

• Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
• Weight ≥ 8.5 kg and ≤ 21 kg at the time of Screening Visit 2
• Naive to treatment or have discontinued an approved drug/therapy

Exclusion:

• Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
• BMI < 3rd percentile
• Participant with history of aspiration pneumonia or signs of aspiration
• Elevated anti-AAV9 antibody
• History of gene therapy, hematopoietic transplantation, or solid organ transplantation
• Inability to take corticosteroids
• Concomitant use of immunosuppressive therapy
• Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
• Awake hypoxemia or awake oxygen saturation level decrease
• Hepatic dysfunction
• Presence of a confirmed or suspected infection
• If previously treated with disease modifying therapy, specified washout times apply
• Documented any parental consanguinity.