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

NCT05073133 | Completed Phase 4 Results DMC

• 2 other identifiers: COAV101A1IC012023-000864-67
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent AEs and SAEs

  An AE is any untoward medical occurrence (eg any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results are reported as Adverse Events if clinically significant and as applicable, per investigator assessment.

  Up to Month 18

• Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest

  An AE is any untoward medical occurrence (eg any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Adverse events of special interest (AESI) are defined by the important identified risk and important potential risk: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These were assessed by the investigator.

  Up to Month 18

Secondary Outcomes (1)

• Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)

  Baseline (Screening), and at Weeks 26, 52 and 78

Study Arms (1)

OAV101

EXPERIMENTAL

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

Genetic: OAV101

Interventions

OAV101 GENETIC

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

Also known as: AVXS-101, Zolgensma

OAV101

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

CABA, Buenos Aires, C1181ACH, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1245AAM, Argentina

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30130-000, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Related Links

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

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Muscular Diseases

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Musculoskeletal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: OAV101 will be administered as a single IV infusion at 1.1e14 vg/kg over approximately 60 minutes

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: October 11, 2021
• Study Start: November 4, 2021
• Primary Completion: August 8, 2023
• Study Completion: August 8, 2023
• Last Updated: October 9, 2024
• Results First Posted: May 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

AR (2); BR (3)