Phase 4
N=16
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA)
Muscular Atrophy, Spinal
Bottom Line
View on ClinicalTrials.gov: NCT05073133 ↗Enrolled (actual)
16
Serious AEs
68.8%
Results posted
May 2024
Primary outcome: Primary: Number of Participants With Treatment Emergent AEs and SAEs — 16; 11; 11; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- OAV101 (Genetic)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Aug 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent AEs and SAEs |
16; 11; 11; 3; 0; 2 | — |
| PRIMARY Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest |
11; 5; 5; 2; 2; 5 | — |
| SECONDARY Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) |
6; 2; 1; 0; 0; 0 | — |
Summary
This was a phase IV Open-label, single-arm, single-dose, multicenter study, to evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene ≤ 24 months and weighing ≤ 17 kg, over a 18-month period post infusion.
Eligibility Criteria
Inclusion Criteria
- Written informed consent/assent obtained prior to any assessment performed
- Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
- Age ≤ 24 months of age at time of treatment
- Weight ≤17 kg at the time of Screening Period 4. Naïve to treatment or have discontinued an approved drug/therapy 5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Key Exclusion Criteria
- Previous use of OAV101 or any AAV9 gene therapy
- Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
- Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
- Anti-AAV9 antibody titer > 1: 50 as determined by ligand binding immunoassay at the time of screening
- Inability to take corticosteroids
- Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
- Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, ≥ ULN; CTCAE ≥ 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
- Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
- Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
Data sourced from ClinicalTrials.gov (NCT05073133). 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.