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

NCT ID: NCT05073133

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-04
• Study Completion Date: 2023-08-08

Brief 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.

Detailed Description

This is an open-label, single arm, multi-center study to evaluate the safety, tolerability, and efficacy of IV OAV101 in symptomatic SMA pediatric participants. The study enrolled participants ≤ 24 months old that weigh ≤ 17 kg. Participants who met eligibility criteria at Screening and Baseline visits received a single dose of IV OAV101 t the approved dose of 1.1e14 vg/kg and were followed for 18 months. The study included a 20-day screening period in which there were 2 Screening visits, during which, eligibility was assessed (Screening 1), weight was collected for dose calculation (Screening 2), and baseline assessments were performed prior to treatment.

On Day -1, participants were admitted to the hospital for pre-treatment baseline procedures including prednisolone treatment per study protocol. On Day 1, participants received a single IV infusion of OAV101. Participants were discharged 12-48 hours after the infusion, based on Investigator judgment. Safety monitoring was performed on an ongoing basis per protocol requirement and was evaluated by the clinical safety team as well as DMC (Data monitoring committee).

Conditions

Muscular Atrophy, Spinal

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OAV101

A single IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes

Group Type: EXPERIMENTAL

OAV101

Intervention Type: GENETIC

A single Gene Therapy IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes

Interventions

OAV101

A single Gene Therapy IV infusion at 1.1e14 vector genome (vg)/kg over approximately 60 minutes

Intervention Type: GENETIC

Other Intervention Names

AVXS-101, Zolgensma

Eligibility Criteria

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

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)

• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Belo Horizonte, Minas Gerais, Brazil

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Countries

Argentina; Brazil

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1876

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

2023-000864-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COAV101A1IC01

Identifier Type: -

Identifier Source: org_study_id