Phase 3
N=24
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Spinal Muscular Atrophy
Bottom Line
View on ClinicalTrials.gov: NCT04851873 ↗Enrolled (actual)
24
Serious AEs
62.5%
Results posted
Jan 2024
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket — 7; 8; 9; 24 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- OAV101 (Genetic)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket |
7; 8; 9; 24; 7; 8 | — |
| PRIMARY Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket |
6; 5; 9; 20; 4; 6 | — |
| PRIMARY Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure |
1; 0; 1; 2; 7; 8 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg) |
5.3; -1.3; 0.4; 1.3; -2.3; -5.6 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg) |
1.7; 4.8; -2.1; 1.3; -3.7; -5.1 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min) |
-1.1; -1.6; 0.8; -0.6; -0.1; -0.1 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min) |
3.3; 6.3; 16.3; 9.2; -1.4; -3.1 | — |
| PRIMARY Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius) |
0.07; -0.11; 0.07; 0.01; 0.11; -0.48 | — |
| PRIMARY Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level |
0.0; -0.3; -0.4; -0.3; 0.3; -0.1 | — |
| SECONDARY Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development. |
7; 8; 9; 24; 7; 8 | — |
| SECONDARY Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age |
3.8; 2.3; 3.1; 3.0; 1.3; 4.5 | — |
| SECONDARY Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age. |
2.8; 1.2; 1.0; 1.4; 4.3; 0.8 | — |
Summary
To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.
Eligibility Criteria
Inclusion
- Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
- Weight ≥ 8.5 kg and ≤ 21 kg at the time of Screening Visit 2
- Naive to treatment or have discontinued an approved drug/therapy
Exclusion:
- Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
- BMI < 3rd percentile
- Participant with history of aspiration pneumonia or signs of aspiration
- Elevated anti-AAV9 antibody
- History of gene therapy, hematopoietic transplantation, or solid organ transplantation
- Inability to take corticosteroids
- Concomitant use of immunosuppressive therapy
- Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
- Awake hypoxemia or awake oxygen saturation level decrease
- Hepatic dysfunction
- Presence of a confirmed or suspected infection
- If previously treated with disease modifying therapy, specified washout times apply
- Documented any parental consanguinity.
Data sourced from ClinicalTrials.gov (NCT04851873). 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.