Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (SPR1NT)

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ClinicalTrials.gov Identifier: NCT03505099

Recruitment Status : Completed

First Posted : April 23, 2018

Results First Posted : January 11, 2022

Last Update Posted : September 7, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

PRA Health Sciences

Information provided by (Responsible Party):

Novartis ( Novartis Gene Therapies )

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Spinal Muscular Atrophy
Intervention	Biological: onasemnogene abeparvovec-xioi
Enrollment	30

Participant Flow

Recruitment Details	A total of 30 participants took part in the trial at 16 sites in the United States, the United Kingdom, Belgium, Canada, Australia and Japan between April 2018 and June 2021.
Pre-assignment Details	A total of 44 participants were screened, of which 14 were screen failures and 30 were enrolled and received study drug. One participant had 4 copies of SMN2. This participant was excluded from all analysis populations and data is not reported due to privacy concerns.


Arm/Group Title	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
Arm/Group Description	Participants with bi-allelic deleti...	Participants with bi-allelic deleti...
Arm/Group Description	Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Period Title: Overall Study
Started	14	15
Received AVXS-101	14	15
Completed	14	15
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2	Total
Arm/Group Description		Participants with bi-allelic deleti...	Participants with bi-allelic deleti...	Total of all reporting groups
Arm/Group Description		Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued	Total of all reporting groups
Overall Number of Baseline Participants		14	15	29
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	15 participants	29 participants
	<=18 years	14 100.0%	15 100.0%	29 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	15 participants	29 participants
	Female	10 71.4%	9 60.0%	19 65.5%
	Male	4 28.6%	6 40.0%	10 34.5%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	15 participants	29 participants
	Hispanic or Latino	4 28.6%	2 13.3%	6 20.7%
	Not Hispanic or Latino	10 71.4%	13 86.7%	23 79.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	14 participants	15 participants	29 participants
Asian		2 14.3%	2 13.3%	4 13.8%
American Indian or Alaska Native		0 0.0%	1 6.7%	1 3.4%
Black or African American		1 7.1%	0 0.0%	1 3.4%
White		7 50.0%	10 66.7%	17 58.6%
Other		4 28.6%	2 13.3%	6 20.7%
SMN2 gene modifier mutation (c.859G>C) Present Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	15 participants	29 participants
		0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1.Primary Outcome


Title	Cohort 1: Number of Participants Who Achieved Sitting Alone for at Least 30 Seconds
Description	Defined by the Bayley Scales of Infant and Toddler Development (BSID) ...
Description	Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (GM) subtest performance criteria number 26, confirmed by video recording, as a participant who sits for at least 30 seconds without assistance from another person or object. The participant was allowed to use their upper extremities.
Time Frame	From Day 1 up to 18 months of age visit

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G>C) who received AVXS-101.


Arm/Group Title	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2
Arm/Group Description:	Participants with bi-allelic deleti...
Arm/Group Description:	Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	14
Measure Type: Count of Participants Unit of Measure: Participants
	14 100.0%

2.Primary Outcome


Title	Cohort 2: Number of Participants Who Achieved Standing Alone for at Least 3 Seconds
Description	Defined by the BSID GM subtest performance criteria number 40, confirm...
Description	Defined by the BSID GM subtest performance criteria number 40, confirmed by video recording, as a participant who stands alone for at least 3 seconds unsupported.
Time Frame	From Day 1 up to 24 months of age visit

Outcome Measure Data

Analysis Population Description

ITT population (cohort 2) - All enrolled participants with bi-allelic SMN1 deletions and 3 copies of SMN2 without the SMN2 gene modifier mutation (c.859G>C) who received AVXS-101.


Arm/Group Title	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
Arm/Group Description:	Participants with bi-allelic deleti...
Arm/Group Description:	Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	15
Measure Type: Count of Participants Unit of Measure: Participants
	15 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	76.5
	Confidence Interval	(2-Sided) 95% 50.95 to 92.21
	Estimation Comments	[Not Specified]

Other Statistical Analysis		Data for the current study were compared to historical control data (Finkel et al, 2014 - PubMed 25080519) where 19 out of 81 participants (23.46%) with 3 copies of SMN2 achieved standing alone for at least 3 seconds.

3.Secondary Outcome


Title	Cohort 1: Event-free Survival at 14 Months of Age
Description	Event-free survival at 14 months of age was defined as the number of p...
Description	Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age.
Time Frame	From Day 1 up to 14 months of age

Outcome Measure Data

Analysis Population Description

ITT population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G>C) who received AVXS-101.


Arm/Group Title	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2
Arm/Group Description:	Participants with bi-allelic deleti...
Arm/Group Description:	Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	14
Measure Type: Count of Participants Unit of Measure: Participants
	14 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	73.9
	Confidence Interval	(2-Sided) 95% 44.67 to 91.61
	Estimation Comments	[Not Specified]

Other Statistical Analysis		Data for the current study were compared to historical control data (Finkel et al 2014 - PubMed 25080519) where 6 out of 23 participants (26.09%) with 2 copies of SMN2 were alive and did not require permanent ventilation.

4.Secondary Outcome


Title	Cohort 1: Number of Participants Who Achieved the Ability to Maintain Weight at or Above the Third Percentile Without the Need for Non-Oral or Mechanical Feeding Support
Description	The ability to maintain weight at or above the third percentile withou...
Description	The ability to maintain weight at or above the third percentile without the need for non-oral or mechanical feeding support was defined by meeting the following criteria at each visit up to 18 months of age: Did not receive nutrition through mechanical support (i.e., feeding tube) Maintained weight (≥ third percentile for age and sex as defined by World Health Organization [WHO] guidelines) consistent with the participant's age at the assessment.
Time Frame	From Day 1 up to 18 months of age

Outcome Measure Data

Analysis Population Description

ITT population (cohort 1) - All enrolled participants with bi-allelic SMN1 deletions and 2 copies of SMN2 without the SMN2 gene modifier mutation (c.859G>C) who received AVXS-101.


Arm/Group Title	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2
Arm/Group Description:	Participants with bi-allelic deleti...
Arm/Group Description:	Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	14
Measure Type: Count of Participants Unit of Measure: Participants
	13 92.9%

5.Secondary Outcome


Title	Cohort 2: Number of Participants Who Achieved the Ability to Walk Alone
Description	Defined by the BSID GM subtest performance criteria number 43, confirm...
Description	Defined by the BSID GM subtest performance criteria number 43, confirmed by video recording, as a participant who takes 5 coordinated independent steps.
Time Frame	From Day 1 up to 24 months of age visit

Outcome Measure Data

Analysis Population Description

ITT population (cohort 2) - All enrolled participants with bi-allelic SMN1 deletions and 3 copies of SMN2 without the SMN2 gene modifier mutation (c.859G>C) who received AVXS-101.


Arm/Group Title	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
Arm/Group Description:	Participants with bi-allelic deleti...
Arm/Group Description:	Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	15
Measure Type: Count of Participants Unit of Measure: Participants
	14 93.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	72.3
	Confidence Interval	(2-Sided) 95% 44.90 to 90.11
	Estimation Comments	[Not Specified]

Other Statistical Analysis		Data for the current study were compared to historical control data (Finkel et al, 2014 - PubMed 25080519) where 17 out of 81 participants (20.99%) with 3 copies of SMN2 achieved the ability to walk alone.

Adverse Events

Time Frame	Cohort 1: Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to the 18 months of age visit. Serious adverse events (SAEs) were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 20 months). Cohort 2: TEAEs were collected from Day 1 up to the 24 months of age visit. SAEs were collected from signing of informed consent to 30 days after the last study visit (up to a maximum of approximately 26 months).
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2		Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
Arm/Group Description	Participants with bi-allelic deleti...		Participants with bi-allelic deleti...
Arm/Group Description	Participants with bi-allelic deletions of survival of motor neuron 1 (SMN1) and 2 copies of SMN2 received a single dose of AVXS-101 administered as an intravenous (IV) infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram) on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.		Participants with bi-allelic deletions of SMN1 and 3 copies of SMN2 received a single dose of AVXS-101 administered as an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1-2 mg/kg/day from 1 day prior to AVXS-101 infusion until at least 30 days post-infusion at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
All-Cause Mortality
	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2		Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/14 (0.00%)		0/15 (0.00%)
Serious Adverse Events Serious Adverse Events
	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2		Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/14 (35.71%)		3/15 (20.00%)
Ear and labyrinth disorders
Middle ear effusion ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Gastrointestinal disorders
Inguinal hernia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Infections and infestations
Croup infectious ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Pyelonephritis ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Ear infection ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Pharyngitis ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Metabolism and nutrition disorders
Hypercalcaemia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Nervous system disorders
Lethargy ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
1 Term from vocabulary, MedDRA (23.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cohort 1: Bi-allelic Deletions of SMN1 and 2 Copies of SMN2		Cohort 2: Bi-allelic Deletions of SMN1 and 3 Copies of SMN2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100.00%)		15/15 (100.00%)
Blood and lymphatic system disorders
Lymphadenopathy ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Microcytic anaemia ^† 1	1/14 (7.14%)	1	2/15 (13.33%)	3
Thrombocytopenia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Iron deficiency anaemia ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Congenital, familial and genetic disorders
Dacryostenosis congenital ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	1
Hydrocele ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Ear and labyrinth disorders
Middle ear effusion ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Ear pain ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	2
Endocrine disorders
Precocious puberty ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Cushingoid ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Eye disorders
Eye discharge ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Chalazion ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Ocular hyperaemia ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Gastrointestinal disorders
Abdominal discomfort ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Constipation ^† 1	4/14 (28.57%)	5	1/15 (6.67%)	1
Diarrhoea ^† 1	3/14 (21.43%)	4	4/15 (26.67%)	5
Dysphagia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Flatulence ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Gastrooesophageal reflux disease ^† 1	3/14 (21.43%)	3	3/15 (20.00%)	4
Gingival pain ^† 1	1/14 (7.14%)	2	0/15 (0.00%)	0
Inguinal hernia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Teething ^† 1	2/14 (14.29%)	2	5/15 (33.33%)	6
Tooth development disorder ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Vomiting ^† 1	3/14 (21.43%)	3	2/15 (13.33%)	2
Abdominal pain upper ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Haematemesis ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Haematochezia ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Nausea ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Regurgitation ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Stomatitis ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
General disorders
Developmental delay ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Influenza like illness ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Malaise ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Pyrexia ^† 1	7/14 (50.00%)	7	11/15 (73.33%)	18
Vessel puncture site bruise ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Immune system disorders
Food allergy ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Infections and infestations
Adenovirus infection ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
COVID-19 ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Candida infection ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Candida nappy rash ^† 1	1/14 (7.14%)	2	0/15 (0.00%)	0
Conjunctivitis ^† 1	1/14 (7.14%)	2	1/15 (6.67%)	2
Croup infectious ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Ear infection ^† 1	2/14 (14.29%)	3	1/15 (6.67%)	3
Fungal infection ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Gastroenteritis viral ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Infected bite ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Influenza ^† 1	2/14 (14.29%)	2	0/15 (0.00%)	0
Nasopharyngitis ^† 1	2/14 (14.29%)	3	3/15 (20.00%)	4
Otitis media ^† 1	1/14 (7.14%)	1	3/15 (20.00%)	6
Pneumonia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Respiratory tract infection ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Respiratory tract infection viral ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	2
Rhinitis ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	1
Rhinovirus infection ^† 1	2/14 (14.29%)	2	0/15 (0.00%)	0
Upper respiratory tract infection ^† 1	5/14 (35.71%)	7	9/15 (60.00%)	13
Viral upper respiratory tract infection ^† 1	3/14 (21.43%)	10	1/15 (6.67%)	1
Bronchitis ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Exanthema subitum ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Fungal skin infection ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Gastroenteritis ^† 1	0/14 (0.00%)	0	2/15 (13.33%)	3
Hand-foot-and-mouth disease ^† 1	0/14 (0.00%)	0	2/15 (13.33%)	2
Otitis media acute ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Respiratory syncytial virus infection ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Roseola ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Urinary tract infection ^† 1	0/14 (0.00%)	0	2/15 (13.33%)	2
Viral infection ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Injury, poisoning and procedural complications
Eye injury ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Skin abrasion ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Tracheal deviation ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Arthropod sting ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Contusion ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Eyelid injury ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Scratch ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Skin wound ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Investigations
Alanine aminotransferase increased ^† 1	1/14 (7.14%)	2	3/15 (20.00%)	5
Aspartate aminotransferase increased ^† 1	3/14 (21.43%)	4	4/15 (26.67%)	6
Blood creatine phosphokinase MB increased ^† 1	1/14 (7.14%)	1	2/15 (13.33%)	2
Blood creatine phosphokinase increased ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Gamma-glutamyltransferase increased ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	1
Head lag ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Platelet count decreased ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Platelet count increased ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	1
Troponin increased ^† 1	1/14 (7.14%)	2	2/15 (13.33%)	2
Bacterial test positive ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	2
Blood alkaline phosphatase increased ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Blood calcium increased ^† 1	0/14 (0.00%)	0	2/15 (13.33%)	2
Carbon dioxide decreased ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Metabolism and nutrition disorders
Failure to thrive ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Hypercalcaemia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Hypomagnesaemia ^† 1	1/14 (7.14%)	2	0/15 (0.00%)	0
Lactose intolerance ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Poor feeding infant ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Weight gain poor ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Musculoskeletal and connective tissue disorders
Hip deformity ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Joint contracture ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Kyphosis ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Loose body in joint ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Pain in extremity ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Nervous system disorders
Areflexia ^† 1	2/14 (14.29%)	2	1/15 (6.67%)	2
Hypertonia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Hypokinesia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Hyporeflexia ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Hypotonia ^† 1	3/14 (21.43%)	5	2/15 (13.33%)	3
Motor developmental delay ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Muscle contractions involuntary ^† 1	3/14 (21.43%)	3	1/15 (6.67%)	1
Tremor ^† 1	3/14 (21.43%)	4	0/15 (0.00%)	0
Febrile convulsion ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Lethargy ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Psychiatric disorders
Irritability ^† 1	1/14 (7.14%)	1	1/15 (6.67%)	2
Agitation ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Renal and urinary disorders
Nephrocalcinosis ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Pyelocaliectasis ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Dysuria ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	1/14 (7.14%)	4	4/15 (26.67%)	6
Nasal congestion ^† 1	3/14 (21.43%)	3	2/15 (13.33%)	2
Rhinorrhoea ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Sleep apnoea syndrome ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Snoring ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Upper respiratory tract congestion ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Skin and subcutaneous tissue disorders
Cafe au lait spots ^† 1	1/14 (7.14%)	1	0/15 (0.00%)	0
Eczema ^† 1	2/14 (14.29%)	2	0/15 (0.00%)	0
Rash ^† 1	3/14 (21.43%)	6	2/15 (13.33%)	2
Blister ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Dermatitis diaper ^† 1	0/14 (0.00%)	0	3/15 (20.00%)	3
Eczema infantile ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Lipohypertrophy ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Miliaria ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Pruritus ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
Rash macular ^† 1	0/14 (0.00%)	0	1/15 (6.67%)	1
1 Term from vocabulary, MedDRA (23.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

Link to the full study results: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17902

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Depending on local requirements, Sponsor's consent necessary before publication of study, or Sponsor can review results communications before public release with a right to request changes to communications regarding trial results between 40 to 60 and up to 90 or 120 days, as applicable, from the time submitted to Sponsor for review to remove references to Sponsor's Confidential Information or delay results communications to permit Sponsor to obtain appropriate Intellectual Property protection.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	EMEA Medical Information
Organization:	Novartis Gene Therapies EU Limited
Phone:	+353 (1) 566-2364
EMail:	medinfoemea.gtx@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Strauss KA, Farrar MA, Muntoni F, Saito K, Mendell JR, Servais L, McMillan HJ, Finkel RS, Swoboda KJ, Kwon JM, Zaidman CM, Chiriboga CA, Iannaccone ST, Krueger JM, Parsons JA, Shieh PB, Kavanagh S, Wigderson M, Tauscher-Wisniewski S, McGill BE, Macek TA. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat Med. 2022 Jul;28(7):1390-1397. doi: 10.1038/s41591-022-01867-3. Epub 2022 Jun 17.

Strauss KA, Farrar MA, Muntoni F, Saito K, Mendell JR, Servais L, McMillan HJ, Finkel RS, Swoboda KJ, Kwon JM, Zaidman CM, Chiriboga CA, Iannaccone ST, Krueger JM, Parsons JA, Shieh PB, Kavanagh S, Tauscher-Wisniewski S, McGill BE, Macek TA. Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial. Nat Med. 2022 Jul;28(7):1381-1389. doi: 10.1038/s41591-022-01866-4. Epub 2022 Jun 17.

Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12. Erratum In: Drug Saf. 2022 Feb;45(2):191-192.

Layout table for additonal information

Responsible Party:	Novartis ( Novartis Gene Therapies )
ClinicalTrials.gov Identifier:	NCT03505099
Other Study ID Numbers:	AVXS-101-CL-304 2017-004087-35 ( EudraCT Number ) JapicCTI-184203 ( Registry Identifier: JapicCTI ) COAV101A12303 ( Other Identifier: Novartis Pharmaceuticals )
First Submitted:	April 13, 2018
First Posted:	April 23, 2018
Results First Submitted:	December 14, 2021
Results First Posted:	January 11, 2022
Last Update Posted:	September 7, 2022

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