Trial Outcomes & Findings for Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA) (NCT NCT05073133)
NCT ID: NCT05073133
Last Updated: 2024-10-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
16 participants
Primary outcome timeframe
Up to Month 18
Results posted on
2024-10-09
Participant Flow
16 participants were enrolled into the study, at five sites from Brazil (three sites) and Argentina (two sites). Six participants were from Argentina and 10 from Brazil.
On Day -1, participants were admitted to the hospital for pre-treatment baseline procedures including prednisolone treatment per study protocol.
Participant milestones
| Measure |
OAV101
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
OAV101
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Overall Study
Death
|
2
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
OAV101
n=16 Participants
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Age, Continuous
Age at dosing
|
15.79 months
STANDARD_DEVIATION 5.89 • n=16 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=16 Participants
|
PRIMARY outcome
Timeframe: Up to Month 18Population: Full analysis set (FAS) - all treated patients.
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.
Outcome measures
| Measure |
OAV101
n=16 Participants
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Number of Participants With Treatment Emergent AEs and SAEs
Any treatment-emergent adverse events
|
16 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Any treatment-emergent adverse events related to OAV101
|
11 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Any serious treatment-emergent adverse events
|
11 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Serious treatment-emergent adverse events related to OAV101
|
3 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Treatment-emergent adverse events leading to study discontinuation
|
0 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Treatment-emergent adverse events leading to death
|
2 Participants
|
|
Number of Participants With Treatment Emergent AEs and SAEs
Treatment-emergent adverse events of special interest
|
12 Participants
|
PRIMARY outcome
Timeframe: Up to Month 18Population: Full analysis set (FAS) - all treated patients.
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.
Outcome measures
| Measure |
OAV101
n=16 Participants
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
Risk name: Hepatotoxicity
|
11 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Aspartate aminotransferase increased
|
5 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Alanine aminotransferase increased
|
5 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Blood alkaline phosphatase increased
|
2 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Bilirubin conjugated increased
|
2 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Gamma-glutamyltransferase increased
|
5 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Hepatic enzyme increased
|
3 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Hepatic failure
|
1 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Transaminases increased
|
2 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
Risk name: Thrombocytopenia
|
5 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Platelet count decreased
|
4 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Thrombocytopenia
|
1 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
Risk name: Thrombotic microangiopathy
|
2 Participants
|
|
Evaluation of Important Identified and Important Potential Risks - Treatment-emergent Adverse Events of Special Interest
-Preferred term: Thrombotic microangiopathy
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline (Screening), and at Weeks 26, 52 and 78Population: Full analysis set (FAS) - all treated patients with evaluable assessments at the respective assessment time points.
The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) was used to measure developmental motor milestones. This was assessed via the milestone checklist. The 6 developmental milestones are: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
Outcome measures
| Measure |
OAV101
n=16 Participants
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Standing with assistance
|
1 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Walking with assistance
|
0 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Standing alone
|
0 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Walking alone
|
0 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Sitting without support (n=14)
|
12 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Hands-and-knees crawling (n=14)
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Standing with assistance (n=14)
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Walking with assistance (n=14)
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Standing alone (n=14)
|
1 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Sitting without support
|
6 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Screening - Hands-and-knees crawling
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 26 Walking alone (n=14)
|
0 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Sitting without support (n=13)
|
10 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Hands-and-knees crawling (n=13)
|
4 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Standing with assistance (n=13)
|
7 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Walking with assistance (n=13)
|
3 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Standing alone (n=13)
|
6 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 52 Walking alone (n=13)
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Sitting without support (n=12)
|
10 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Hands-and-knees crawling (n=12)
|
3 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Standing with assistance (n=12)
|
7 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Walking with assistance (n=12)
|
2 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Standing alone (n=12)
|
3 Participants
|
|
Number of Participants Who Achieve Development Motor Milestones According to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Week 78 Walking alone (n=12)
|
1 Participants
|
Adverse Events
OAV101A1 1.le 14vg/kg All
Serious events: 11 serious events
Other events: 16 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
OAV101A1 1.le 14vg/kg All
n=16 participants at risk
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
General disorders
Pyrexia
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Hepatobiliary disorders
Hepatic failure
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Bronchiolitis
|
18.8%
3/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
COVID-19
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Gastroenteritis
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Respiratory tract infection
|
18.8%
3/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Renal and urinary disorders
Renal failure
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
Other adverse events
| Measure |
OAV101A1 1.le 14vg/kg All
n=16 participants at risk
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
|
|---|---|
|
Investigations
Blood lactate dehydrogenase increased
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Gamma-glutamyltransferase increased
|
31.2%
5/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Hepatic enzyme increased
|
18.8%
3/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Platelet count decreased
|
25.0%
4/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Constipation
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Stomatitis
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Gastrointestinal disorders
Vomiting
|
43.8%
7/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
General disorders
Pyrexia
|
43.8%
7/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Immune system disorders
Hypersensitivity
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Asymptomatic bacteriuria
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
COVID-19
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Conjunctivitis
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Coxsackie viral infection
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Gastroenteritis
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Influenza
|
18.8%
3/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Pneumonia
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Pneumonia bacterial
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Rhinitis
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Urinary tract infection
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Infections and infestations
Viral infection
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Alanine aminotransferase increased
|
31.2%
5/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Aspartate aminotransferase increased
|
31.2%
5/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Bilirubin conjugated increased
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Blood alkaline phosphatase increased
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
Transaminases increased
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Investigations
White blood cell count increased
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Psychiatric disorders
Irritability
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Catarrh
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
4/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngitis
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillitis
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
12.5%
2/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
6.2%
1/16 • Adverse events are reported from the single dose of study treatment plus 18 months post treatment, up to a maximum duration of 18 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER