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

Plain-language summary

This study examined the safety and efficacy of intravenous OAV101 gene therapy in children with spinal muscular atrophy (SMA). It enrolled children with SMA confirmed by biallelic SMN1 mutations who were up to 24 months of age and under 17 kg at the time of treatment. It was a Phase 4 study and is completed.

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

Trial details

Phase

Phase 4

Status

Completed

Sponsor

Novartis Pharmaceuticals

Intervention

OAV101

Start date

11/4/2021

Estimated completion

8/8/2023

Countries

Argentina, Brazil

Related genes

Locations

• CABA, Argentina
• Buenos Aires, Argentina
• Belo Horizonte, Brazil
• Porto Alegre, Brazil
• São Paulo, Brazil

Eligibility criteria

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

Inclusion Criteria:

1. Written informed consent/assent obtained prior to any assessment performed
2. Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
3. Age ≤ 24 months of age at time of treatment

3\. 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:

1. Previous use of OAV101 or any AAV9 gene therapy
2. Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
3. Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
4. Anti-AAV9 antibody titer \> 1:50 as determined by ligand binding immunoassay at the time of screening
5. Inability to take corticosteroids
6. 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)
7. 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)
8. Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
9. Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)