NCT05089656

Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA)

A Randomized, Sham-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Intrathecal OAV101 in Type 2 Spinal Muscular Atrophy (SMA) Patients Who Are ≥ 2 to < 18 Years of Age, Treatment Naive, Sitting, and Never Ambulatory

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 126 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase III multi-center, single dose (1.2 x 10\^14 vector genomes), randomized, sham controlled, double-blind study that investigates the efficacy, safety and tolerability of OAV101B in treatment naive, sitting and never ambulatory SMA patients 2 to \<18 years of age.

Detailed description

Eligible participants received a single administration of OAV101B at the dose of 1.2 x 10\^14 vector genomes intrathecally or the sham procedure on Day 1 (Treatment Period 1), and were followed for a period of 52 weeks for Period 1. In Period 2, participants who received the sham treatment in Period 1 were administered OAV101B, and participants who received OAV101B in Period 1 underwent the sham procedure. Participants were followed up for 12 weeks in Period 2. The study consisted of a Screening and Baseline Period followed by two Treatment and Follow-up Periods. Participants were admitted to the hospital on Day 1 (or Day -1 as per local standards of care). After receiving OAV101B or the sham procedure on Day 1, participants underwent in-patient safety monitoring through Day 2 and optionally for Day 3. After Period 1, eligible participants could continue to Period 2 subsequently entering Period 2 in a rolling seamless fashion as participants completed Follow-up Period 1. In Treatment Period 2, eligible participants who received a sham procedure on Study Day 1 of Treatment Period 1 were hospitalized to receive OAV101B on Week 52 + 1 day and participants who received OAV101B on Study Day 1 of Treatment Period 1 were hospitalized to receive a sham procedure on the Week 52 + 1 Day. The total duration of the study including both Period 1 and Period 2 was 64 weeks. At the end of the study, all participants who received OAV101B were eligible to enroll in a long-term follow-up study to monitor long-term safety and efficacy. Approximately 125 participants were planned to be randomized in a 3:2 ratio to receive OAV101B (N= \~75) or a sham procedure (N= \~50). The unequal randomization ratio allowed more participants to receive active treatment in Period 1. It was anticipated that approximately 65 randomized participants would be aged 2 to \<5 years and approximately 60 randomized participants would be aged 5 to \<18 years.

Conditions

• Type 2 Spinal Muscular Atrophy

Interventions

Type	Name	Description
GENETIC	OAV101	Gene therapy
PROCEDURE	Sham control	The sham procedure will consist of a small needle prick on the lower back at the location where the LP injection is normally made. The needle will break the skin, but no needle insertion for lumbar puncture will occur.

Timeline

• Start date: 2022-02-01
• Primary completion: 2024-11-12
• Completion: 2025-04-29
• First posted: 2021-10-22
• Last updated: 2026-01-13
• Results posted: 2025-12-08

Locations

42 sites across 13 countries: United States, Brazil, China, Denmark, India, Malaysia, Mexico, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Vietnam

Regulatory

• FDA-regulated drug study