Clinical trial NCT05073133: Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA)
Official title: A Phase IV Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the saFEty, toLerability and effIcacy of Gene Replacement Therapy With intravenousOAV101(AVXS101) in Pediatric Patients From Latin America With Spinal Muscular Atrophy (SMA) - OFELIA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Muscular Atrophy, Spinal
Keywords: Zolgensma
OAV101
AVXS 101
gene therapy
Muscle atrophy
SBMA
spinal and bulbar muscular atrophy
spinal muscular atrophy
bulbar muscular atrophy
muscle function
myopathy
muscle wasting
atrophied muscle
loss of muscle strength
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-10-11
Enrollment: 16
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: OAV101 will be administered as a single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
Primary purpose: TREATMENT

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).

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

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)

Primary outcomes:
measure: Number of Participants With Treatment Emergent AEs and SAEs
timeFrame: Up to Month 18
measure: Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
timeFrame: Up to Month 18
Secondary outcomes:
measure: Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
timeFrame: Baseline (Screening), and at Weeks 26, 52 and 78
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
Study officials:
References: