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

Plain-language summary

This Phase 3 study investigated the efficacy, safety, and tolerability of a single intrathecal dose (1.2 x 10^14 vector genomes) of OAV101 (Zolgensma, AVXS-101) in children with type 2 spinal muscular atrophy (SMA). It used a multi-center, randomized, sham-controlled, double-blind design. Participants were treatment-naive patients aged 2 to under 18 with confirmed 5q SMA who could sit but had never walked, whose clinical signs began at 6 months of age or later, and who had never used SMN-targeting therapies such as risdiplam (Evrysdi) or nusinersen (Spinraza).

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 3

Status

Completed

Sponsor

Novartis Pharmaceuticals

Intervention

OAV101 (Zolgensma, AVXS-101), Sham control

Start date

2/1/2022

Estimated completion

4/29/2025

Countries

United States, Brazil, China, Denmark, India, Malaysia, Mexico, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Vietnam

Related genes

Locations

• Farmington, United States
• Chicago, United States
• Strasburg, United States
• Memphis, United States
• Norfolk, United States
• Norfolk, United States
• Curitiba, Brazil
• São Paulo, Brazil
• Beijing, China
• Chongqing, China
• Guangzhou, China
• Shenzhen, China
• Chengdu, China
• Hangzhou, China
• Beijing, China
• Beijing, China
• Beijing, China
• Copenhagen, Denmark
• Copenhagen, Denmark
• New Delhi, India
• New Delhi, India
• New Delhi, India
• New Delhi, India
• Kolkata, India
• Hyderabad, India
• Mumbai, India
• Mumbai, India
• Kuala Lumpur, Malaysia
• Kuala Lumpur, Malaysia
• Guadalajara, Mexico
• Guadalajara, Mexico
• Mexico City, Mexico
• Riyadh, Saudi Arabia
• Singapore, Singapore
• Cape Town, South Africa
• Cape Town, South Africa
• Kaohsiung City, Taiwan
• Kaohsiung City, Taiwan
• Bangkok, Thailand
• Bangkok, Thailand

+2

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Key Inclusion criteria:

* Diagnostic confirmation during screening period of 5q SMA
* The patient must be treatment naive (historical or current use) for all SMN-targeting therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)).
* Onset of clinical signs and symptoms at ≥ 6 months of age
* A complete Hammersmith Functional Motor Scale - Expanded (HFMSE) assessment during the screening period for trial eligibility
* Able to sit independently at screening, but has never had the ability to walk independently.

Key Exclusion criteria:

* Anti-adeno-associated virus serotype 9 (AAV9) antibody titer reported as elevated (reference to \> 1:50 or validated result consistent with being elevated) at screening as determined by sponsor designated lab.
* Infectious process (e.g., viral, bacterial) or febrile illness within 30 days prior to OAV101 treatment or sham procedure
* Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH), \> upper limit of normal (ULN).
* Requiring invasive ventilation, awake noninvasive ventilation for \> 6 hours during a 24-hour period, noninvasive ventilation for \> 12 hours during a 24-hour period or requiring tracheostomy
* Complications at screening that would interfere with motor efficacy assessments including but not limited to, severe contractures or Cobb angle \> 40 in a sitting position
* Surgery for scoliosis or hip fixation in the 12 months prior to Screening or planned within the next 64 weeks
* Clinically significant sensory abnormalities in the neurological examination at Screening