Trial Outcomes & Findings for Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1 (NCT NCT03306277)
NCT ID: NCT03306277
Last Updated: 2026-01-26
Results Overview
Independent sitting is defined as sitting up straight with head erect for at least 30 seconds. This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
22 participants
Primary outcome timeframe
Up to 18 months
Results posted on
2026-01-26
Participant Flow
22 participants were recruited across 16 study centers in the United States.
A screening period of up to 30 days occurred before treatment.
Participant milestones
| Measure |
Onasemnogene Abeparvovec-xioi
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Overall Study
STARTED
|
22
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Onasemnogene Abeparvovec-xioi
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
|
Overall Study
Death
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1
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1
Baseline characteristics by cohort
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 Participants
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Age, Categorical
<=18 years
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22 Participants
n=25 Participants
|
|
Age, Categorical
Between 18 and 65 years
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0 Participants
n=25 Participants
|
|
Age, Categorical
>=65 years
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0 Participants
n=25 Participants
|
|
Age, Continuous
|
3.7 months
STANDARD_DEVIATION 1.6 • n=25 Participants
|
|
Sex: Female, Male
Female
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12 Participants
n=25 Participants
|
|
Sex: Female, Male
Male
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10 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=25 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Black or African American
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3 Participants
n=25 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=25 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=25 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=25 Participants
|
|
Region of Enrollment
United States
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22 participants
n=25 Participants
|
|
Patient reported hospitalizations
Yes
|
17 participants
n=25 Participants
|
|
Patient reported hospitalizations
No
|
5 participants
n=25 Participants
|
|
Weight at baseline
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5.8 kg
STANDARD_DEVIATION 1.1 • n=25 Participants
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|
Height/length at baseline
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61.3 cm
STANDARD_DEVIATION 4.3 • n=25 Participants
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PRIMARY outcome
Timeframe: Up to 18 monthsIndependent sitting is defined as sitting up straight with head erect for at least 30 seconds. This endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance, was the endpoint of event-free survival assessed.
Outcome measures
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 Participants
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Achievement of Independent Sitting for at Least 30 Seconds
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13 Participants
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PRIMARY outcome
Timeframe: 14 monthsSurvival is defined by the avoidance of combined endpoint of either death or permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation is considered a surrogate for death. An acute reversible illness is defined as any condition other than SMA that results in increased medical intervention. The endpoint is a co-primary endpoint. The two co-primary efficacy endpoints were assessed in sequence: The endpoint of functional independent sitting was assessed first and, only when this assessment met statistical significance was the survival endpoint assessed.
Outcome measures
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 Participants
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Event-free Survival
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20 Participants
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SECONDARY outcome
Timeframe: 18 monthsAbility to thrive is defined as achieving all of the following at 18 months of age: * does not receive nutrition through mechanical support or other non-oral method * ability to tolerate thin liquids as demonstrated through a formal swallowing test * maintains weight This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.
Outcome measures
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 Participants
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Ability to Thrive
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9 Participants
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SECONDARY outcome
Timeframe: Up to 18 monthsVentilatory support independence is defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, through assessment of actual usage data captured from the device (Phillips Trilogy BiPAP device). This endpoint is derived solely from the Phillips Trilogy BiPAP device. This is a co-secondary endpoint. The two co-secondary endpoints were assessed in sequence: The endpoint of ability to thrive was assessed first and, only when this assessment met statistical significance was the endpoint of ventilatory support independence assessed.
Outcome measures
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 Participants
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Ventilatory Support Independence
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18 Participants
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Adverse Events
Onasemnogene Abeparvovec-xioi
Serious events: 10 serious events
Other events: 22 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 participants at risk
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Investigations
Alanine aminotransferase increased
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Investigations
Aspartate aminotransferase increased
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Investigations
Human metapneumovirus test positive
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Investigations
Transaminases increased
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Cardiac disorders
Cyanosis
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
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18.2%
4/22 • Number of events 7 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
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9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
4.5%
1/22 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Nervous system disorders
Hydrocephalus
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Gastrointestinal disorders
Dysphagia
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
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Product Issues
Device malfunction
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Metabolism and nutrition disorders
Abnormal weight gain
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Metabolism and nutrition disorders
Failure to thrive
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Metabolism and nutrition disorders
Feeding disorder
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Bronchiolitis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Pneumonia
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Bacterial tracheitis
|
4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Device related infection
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Pneumonia bacterial
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Rhinovirus infection
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4.5%
1/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Sepsis
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4.5%
1/22 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Upper respiratory tract infection
|
4.5%
1/22 • Number of events 1 • Up to 18 months
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Other adverse events
| Measure |
Onasemnogene Abeparvovec-xioi
n=22 participants at risk
One-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose.
Onasemnogene Abeparvovec-xioi: Non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
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|---|---|
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Respiratory, thoracic and mediastinal disorders
Respiration abnormal
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22.7%
5/22 • Number of events 6 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
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13.6%
3/22 • Number of events 3 • Up to 18 months
|
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Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
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13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory track congestion
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Nervous system disorders
Muscle contractions involuntary
|
9.1%
2/22 • Number of events 3 • Up to 18 months
|
|
Gastrointestinal disorders
Constipation
|
40.9%
9/22 • Number of events 11 • Up to 18 months
|
|
Gastrointestinal disorders
Teething
|
22.7%
5/22 • Number of events 6 • Up to 18 months
|
|
Gastrointestinal disorders
Diarrhoea
|
18.2%
4/22 • Number of events 4 • Up to 18 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
18.2%
4/22 • Number of events 4 • Up to 18 months
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
4/22 • Number of events 8 • Up to 18 months
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Gastrointestinal disorders
Dysphagia
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Gastrointestinal disorders
Haematochezia
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.7%
5/22 • Number of events 5 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Eczema
|
13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
9.1%
2/22 • Number of events 3 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
9.1%
2/22 • Number of events 4 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
40.9%
9/22 • Number of events 12 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Deformity thorax
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Joint contracture
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Kyphosis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Torticollis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Metabolism and nutrition disorders
Feeding disorder
|
13.6%
3/22 • Number of events 4 • Up to 18 months
|
|
Metabolism and nutrition disorders
Weight gain poor
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Upper respiratory tract infection
|
50.0%
11/22 • Number of events 28 • Up to 18 months
|
|
Infections and infestations
Conjunctivitis
|
13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Infections and infestations
Otitis media
|
13.6%
3/22 • Number of events 4 • Up to 18 months
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
9.1%
2/22 • Number of events 3 • Up to 18 months
|
|
Infections and infestations
Gastroenteritis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Vascular disorders
Diastolic hypertension
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
General disorders
Pyrexia
|
54.5%
12/22 • Number of events 26 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Use of accessory respiratory muscles
|
22.7%
5/22 • Number of events 7 • Up to 18 months
|
|
Injury, poisoning and procedural complications
Contusion
|
18.2%
4/22 • Number of events 4 • Up to 18 months
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
13.6%
3/22 • Number of events 7 • Up to 18 months
|
|
Investigations
Aspartate aminotransferase increased
|
27.3%
6/22 • Number of events 9 • Up to 18 months
|
|
Investigations
Alanine aminotransferase increased
|
22.7%
5/22 • Number of events 8 • Up to 18 months
|
|
Investigations
Blood creatine phosphokinase MB increased
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Investigations
Lymphocyte count decreased
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Investigations
Weight decreased
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Cardiac disorders
Pericardial effusion
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Congenital, familial and genetic disorders
Pectus excavatum
|
13.6%
3/22 • Number of events 3 • Up to 18 months
|
|
Congenital, familial and genetic disorders
Asphyxiating thoracic dystrophy
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Congenital, familial and genetic disorders
Cryptorchism
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Congenital, familial and genetic disorders
High arched palate
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.1%
2/22 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
31.8%
7/22 • Number of events 10 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
27.3%
6/22 • Number of events 10 • Up to 18 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor can review results communications prior to public release and has right to request changes to communications regarding trial results for a period that is more or equal to 30 days but less than or equal to 150 days from the time submitted to the Sponsor for review in order to either delete references to Sponsor's Confidential Information or delay such results communications to permit Sponsor to obtain appropriate Intellectual Property protection as set forth in the agreement.
- Publication restrictions are in place
Restriction type: OTHER