Phase 3
N=126
Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA)
Type 2 Spinal Muscular Atrophy
Bottom Line
View on ClinicalTrials.gov: NCT05089656 ↗Enrolled (actual)
126
Serious AEs
29.2%
Results posted
Dec 2025
Primary outcome: Primary: Change From Baseline at the End of Period 1 in the Hammersmith Functional Motor Scale Expanded - Total Score - in the ≥ 2 to < 18 Years Age Group — 2.39; 0.51 Scores on a scale — p=0.0074
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- OAV101 (Genetic); Sham control (Procedure)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline at the End of Period 1 in the Hammersmith Functional Motor Scale Expanded - Total Score - in the ≥ 2 to < 18 Years Age Group |
2.39; 0.51 | 0.0074 sig |
| SECONDARY Change From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group |
3.00; 1.56 | 0.1097 |
| SECONDARY Change From Baseline in Revised Upper Limb Module (RULM) Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 18 Years Age Group |
2.44; 0.92 | 0.0122 sig |
| SECONDARY Change From Baseline in the RULM Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group |
3.27; 1.82 | 0.0873 |
| SECONDARY % of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in the ≥ 2 to < 18 Years Age Group |
39.2; 26.0 | 0.0879 |
| SECONDARY % of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 for Participants Aged ≥ 2 to < 5 Years |
48.8; 37.9 | 0.6448 |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events |
74; 46; 104; 27; 5; 36 | — |
| SECONDARY Number of Participants With Adverse Events of Special Interest (AESI) |
7; 5; 10; 4; 2; 9 | — |
| SECONDARY Number (and Percentage) of Patients With Intracardiac Thrombi |
0; 1; 1 | — |
| SECONDARY Number(and Percentage) of Patients With Low Cardiac Function |
8; 9; 17 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT05089656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.