Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy (STRONG)

• ClinicalTrials.gov Identifier: NCT03381729
• Recruitment Status: Terminated
• First Posted: December 22, 2017
• Results First Posted: February 16, 2023
• Last Update Posted: April 24, 2023
• Sponsor: Novartis Gene Therapies
• Information provided by (Responsible Party): Novartis ( Novartis Gene Therapies )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Spinal Muscular Atrophy
• Intervention: Biological: Onasemnogene Abeparvovec-xioi
• Enrollment: 32

Participant Flow

Recruitment Details	A total of 32 participants took part in the trial at 11 sites in the United States between December 2017 and May 2021.
Pre-assignment Details	A total of 38 participants were screened, of which 6 were screen failures and 32 were enrolled and received study drug.

Arm/Group Title	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months	Cohort 3: 2.4E14 vg - Age 24 to <60 Months
Arm/Group Description	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing were planned to receive a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants were also planned to receive daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could have been tapered downwards. At week 9, prednisolone could have been discontinued. Due to early termination of the study, no participants aged 24 to <60 months were enrolled in Cohort 3.
Period Title: Overall Study
Started	3	13	12	4	0
Received AVXS-101	3	13	12	4	0
Completed	3	13	12	4	0
Not Completed	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months	Total
Arm/Group Description		Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection 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		3	13	12	4	32
Baseline Analysis Population Description		Safety Analysis Set: All participants given an AVXS-101 intrathecal injection. Participants were analyzed according to actual dose received.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	12 participants	4 participants	32 participants
	<=18 years	3 100.0%	13 100.0%	12 100.0%	4 100.0%	32 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	3 participants	13 participants	12 participants	4 participants	32 participants
		17.2 (4.1)	16.7 (4.5)	37.5 (10.6)	16.9 (5.6)	24.6 (12.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	12 participants	4 participants	32 participants
	Female	2 66.7%	6 46.2%	6 50.0%	0 0.0%	14 43.8%
	Male	1 33.3%	7 53.8%	6 50.0%	4 100.0%	18 56.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	12 participants	4 participants	32 participants
	Hispanic or Latino	2 66.7%	3 23.1%	0 0.0%	0 0.0%	5 15.6%
	Not Hispanic or Latino	1 33.3%	10 76.9%	12 100.0%	4 100.0%	27 84.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	3 participants	13 participants	12 participants	4 participants	32 participants
White		2 66.7%	10 76.9%	8 66.7%	3 75.0%	23 71.9%
Asian		0 0.0%	1 7.7%	4 33.3%	1 25.0%	6 18.8%
Other		0 0.0%	1 7.7%	0 0.0%	0 0.0%	1 3.1%
Multiple		1 33.3%	1 7.7%	0 0.0%	0 0.0%	2 6.3%

Outcome Measures

1. Primary Outcome

Title	Age 6 to <24 Months Only: Number of Participants Who Achieved the Ability to Stand Alone
Description	Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (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 Month 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Set: All enrolled participants who were given an AVXS-101 intrathecal injection. Participants were analyzed according to the assigned dose. Data were only collected in participants aged 6 to <24 months at time of dosing.

Arm/Group Title	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
Arm/Group Description:	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	3	13	4
Measure Type: Count of Participants; Unit of Measure: Participants
Able to Stand Alone	1 33.3%	1 7.7%	0 0.0%
Unable to Stand Alone	2 66.7%	12 92.3%	4 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: 1.2E14 vg - Age 6 to <24 Months
	Comments	Difference in the percentage of participants who achieved the ability to stand alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.9999
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percent
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -21.8 to 22.8
	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 7 (13.7%) participants achieved the ability to stand alone and 44 (86.3%) participants did not achieve the ability to stand alone.

2. Primary Outcome

Title	Age 24 to <60 Months Only: Change From Baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) Score at Month 12
Description	The HFMSE contained 33 items which were scored on a scale of 0-2 with a total achievable score ranging from 0, if all activities are failed, to 66, if all the activities are achieved. A positive change from baseline indicates a better outcome.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT Set: All enrolled participants who were given an AVXS-101 intrathecal injection. Participants were analyzed according to the assigned dose. Data were only collected in participants aged 24 to <60 months at time of dosing.

Arm/Group Title	Cohort 2: 1.2E14 vg - Age 24 to <60 Months
Arm/Group Description:	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	12
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
	6.0; (3.7 to 8.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: 1.2E14 vg - Age 24 to <60 Months
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0027
	Comments	[Not Specified]
	Method	Mixed-Model Repeat Measure
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference Between Least Squares Mean
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; 1.9 to 9.0
	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 the least squares mean (95% confidence interval) of the change from baseline in HFMSE scores at 12 months was 0.5 (-2.2 to 3.2).

3. Primary Outcome

Title	Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Description	A TEAE was defined as any event that began or worsened in severity on or after the administration of AVXS-101 through the last study visit. Evaluation of TEAEs included the number of participants with at least one: TEAE; Serious TEAE; TEAE related to AVXS-101; TEAE with Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (grade 3 = severe or medically significant to grade 5 = death related to TEAE)
Time Frame	Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: All participants given an AVXS-101 intrathecal injection. Participants were analyzed according to actual dose received.

Arm/Group Title	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
Arm/Group Description:	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	3	13	12	4
Measure Type: Count of Participants; Unit of Measure: Participants
TEAE	3 100.0%	13 100.0%	12 100.0%	4 100.0%
Serious TEAE	1 33.3%	2 15.4%	4 33.3%	0 0.0%
TEAE Related to AVXS-101	0 0.0%	7 53.8%	4 33.3%	1 25.0%
TEAE with CTCAE Grade ≥ 3	1 33.3%	4 30.8%	4 33.3%	0 0.0%

4. Secondary Outcome

Title	Number of Participants Who Achieved the Ability to Walk Alone
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 Month 12

Outcome Measure Data

Analysis Population Description

ITT Set: All enrolled participants who were given an AVXS-101 intrathecal injection. Participants were analyzed according to the assigned dose.

Arm/Group Title	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
Arm/Group Description:	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed	3	13	12	4
Measure Type: Count of Participants; Unit of Measure: Participants
Able to Walk Alone	0 0.0%	1 7.7%	0 0.0%	0 0.0%
Unable to Walk Alone	3 100.0%	12 92.3%	12 100.0%	4 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: 1.2E14 vg - Age 6 to <24 Months
	Comments	Difference in the percentage of participants who achieved the ability to walk alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.9999
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -17.2 to 27.0
	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 5 (9.8%) participants achieved the ability to walk alone and 46 (90.2%) participants did not achieve the ability to walk alone.

5. Secondary Outcome

Title	Average Number of Hours Per Day of Non-invasive Ventilatory Support
Description	Participants were assessed by a pulmonologist and may have been fitted with a non-invasive positive pressure ventilatory (e.g., Bilevel Positive Airway Pressure BiPAP) at the discretion of the pulmonologist and/or investigator. The number of hours per day of non-invasive ventilatory support was captured continuously by the device.
Time Frame	Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

Outcome Measure Data

Analysis Population Description

Data were only collected in participants requiring BiPAP support.

Arm/Group Title		Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
Arm/Group Description:		Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
Overall Number of Participants Analyzed		0	1	1	0
Mean (Standard Deviation); Unit of Measure: hours/day
Month 2	Number Analyzed	0 participants	0 participants	1 participants	0 participants
				10.530 [1] (NA)
Month 3	Number Analyzed	0 participants	0 participants	1 participants	0 participants
				2.930 [1] (NA)
Month 4	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			0.000 [1] (NA)	5.860 [1] (NA)
Month 5	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			0.000 [1] (NA)	4.610 [1] (NA)
Month 6	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			2.590 [1] (NA)	4.490 [1] (NA)
Month 7	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			4.550 [1] (NA)	7.490 [1] (NA)
Month 8	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			7.170 [1] (NA)	8.290 [1] (NA)
Month 9	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			8.690 [1] (NA)	7.690 [1] (NA)
Month 10	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			10.320 [1] (NA)	9.900 [1] (NA)
Month 11	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			14.050 [1] (NA)	3.460 [1] (NA)
Month 12	Number Analyzed	0 participants	1 participants	1 participants	0 participants
			10.120 [1] (NA)	0.040 [1] (NA)

[1]

Only 1 participant had available data so standard deviation could not be calculated.

Adverse Events

Time Frame	Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3)
Adverse Event Reporting Description	Safety Analysis Set: All participants given an AVXS-101 intrathecal injection. Participants were analyzed according to actual dose received.
Arm/Group Title	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
Arm/Group Description	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 6.0E13 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 24 to <60 months at time of AVXS-101 dosing received a single 1.2E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.	Participants aged 6 to <24 months at time of AVXS-101 dosing received a single 2.4E14 vg dose of AVXS-101 administered as an intrathecal injection on Day 1 of the overall study. Participants also received daily doses of prophylactic oral prednisolone starting at a dose of 1 mg/kg/day from 1 day prior to AVXS-101 injection until at least 30 days post-injection at which point the prednisolone dose could be tapered downwards. At week 9, prednisolone could be discontinued.
All-Cause Mortality
	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Serious Adverse Events
	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/3 (33.33%)	2/13 (15.38%)	4/12 (33.33%)	0/4 (0.00%)
Infections and infestations
Bronchitis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Influenza † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Pneumonia † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Pneumonia respiratory syncytial viral † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Respiratory tract infection viral † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Rhinovirus infection † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Investigations
Blood alkaline phosphatase increased † 1	1/3 (33.33%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Alanine aminotransferase increased † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Aspartate aminotransferase increased † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Asthma † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Respiratory failure † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
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: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 6 to <24 Months	Cohort 2: 1.2E14 vg - Age 24 to <60 Months	Cohort 3: 2.4E14 vg - Age 6 to <24 Months
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	13/13 (100.00%)	12/12 (100.00%)	4/4 (100.00%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	0/3 (0.00%)	2/13 (15.38%)	1/12 (8.33%)	0/4 (0.00%)
Leukopenia † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Cardiac disorders
Tachycardia † 1	0/3 (0.00%)	2/13 (15.38%)	2/12 (16.67%)	0/4 (0.00%)
Mitral valve incompetence † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Sinus tachycardia † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Cardiomegaly † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Pericardial effusion † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Pulmonary valve incompetence † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Congenital, familial and genetic disorders
Pectus carinatum † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Pectus excavatum † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Ear and labyrinth disorders
Ear discomfort † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Motion sickness † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Endocrine disorders
Cushingoid † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Gastrointestinal disorders
Vomiting † 1	0/3 (0.00%)	5/13 (38.46%)	3/12 (25.00%)	2/4 (50.00%)
Constipation † 1	0/3 (0.00%)	2/13 (15.38%)	3/12 (25.00%)	2/4 (50.00%)
Teething † 1	1/3 (33.33%)	2/13 (15.38%)	0/12 (0.00%)	1/4 (25.00%)
Abdominal pain † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Anal fissure † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Dental caries † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Diarrhoea † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Dysphagia † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Gastrooesophageal reflux disease † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Haematochezia † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Tooth resorption † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
General disorders
Pyrexia † 1	3/3 (100.00%)	6/13 (46.15%)	7/12 (58.33%)	2/4 (50.00%)
Application site irritation † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Infusion site bruising † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Hepatobiliary disorders
Hepatomegaly † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Immune system disorders
Seasonal allergy † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	1/4 (25.00%)
Hypersensitivity † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Infections and infestations
Upper respiratory tract infection † 1	2/3 (66.67%)	10/13 (76.92%)	5/12 (41.67%)	3/4 (75.00%)
Nasopharyngitis † 1	0/3 (0.00%)	3/13 (23.08%)	2/12 (16.67%)	1/4 (25.00%)
Otitis media † 1	1/3 (33.33%)	0/13 (0.00%)	3/12 (25.00%)	0/4 (0.00%)
Viral infection † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	1/4 (25.00%)
Conjunctivitis † 1	0/3 (0.00%)	2/13 (15.38%)	0/12 (0.00%)	0/4 (0.00%)
Ear infection † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Pneumonia † 1	1/3 (33.33%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Bacteriuria † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Coxsackie viral infection † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Croup infectious † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Furuncle † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Gastroenteritis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Gastroenteritis viral † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Metapneumovirus infection † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Parainfluenzae virus infection † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Pharyngitis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Pharyngitis streptococcal † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Respiratory tract infection viral † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Rhinovirus infection † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Viral pharyngitis † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Viral rash † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Viral upper respiratory tract infection † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Injury, poisoning and procedural complications
Arthropod bite † 1	0/3 (0.00%)	3/13 (23.08%)	0/12 (0.00%)	0/4 (0.00%)
Contusion † 1	0/3 (0.00%)	2/13 (15.38%)	0/12 (0.00%)	0/4 (0.00%)
Skin abrasion † 1	0/3 (0.00%)	0/13 (0.00%)	2/12 (16.67%)	0/4 (0.00%)
Fall † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Investigations
Blood alkaline phosphatase increased † 1	0/3 (0.00%)	2/13 (15.38%)	0/12 (0.00%)	1/4 (25.00%)
Activated partial thromboplastin time prolonged † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Aspartate aminotransferase increased † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Blood creatine phosphokinase MB increased † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Blood iron decreased † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Blood lead increased † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Blood pressure diastolic increased † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Cardiac murmur † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Carnitine decreased † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Crystal urine present † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Electrocardiogram QT prolonged † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Eosinophil count increased † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Neutrophil count increased † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Norovirus test positive † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Respirovirus test positive † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Metabolism and nutrition disorders
Weight gain poor † 1	0/3 (0.00%)	3/13 (23.08%)	0/12 (0.00%)	0/4 (0.00%)
Dehydration † 1	0/3 (0.00%)	0/13 (0.00%)	2/12 (16.67%)	0/4 (0.00%)
Decreased appetite † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Feeding disorder † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Malnutrition † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Metabolic acidosis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Vitamin D deficiency † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Musculoskeletal and connective tissue disorders
Scoliosis † 1	0/3 (0.00%)	0/13 (0.00%)	4/12 (33.33%)	0/4 (0.00%)
Joint contracture † 1	0/3 (0.00%)	0/13 (0.00%)	2/12 (16.67%)	0/4 (0.00%)
Kyphosis † 1	0/3 (0.00%)	2/13 (15.38%)	0/12 (0.00%)	0/4 (0.00%)
Limb asymmetry † 1	1/3 (33.33%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Pain in extremity † 1	0/3 (0.00%)	0/13 (0.00%)	2/12 (16.67%)	0/4 (0.00%)
Arthralgia † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Back pain † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Joint stiffness † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Knee deformity † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Kyphoscoliosis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Mastication disorder † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Muscle contracture † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Muscle tightness † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Soft tissue swelling † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Tendinous contracture † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Tendon discomfort † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Nervous system disorders
Headache † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Language disorder † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Migraine † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Muscle contractions involuntary † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Tremor † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Psychiatric disorders
Irritability † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Sleep terror † 1	1/3 (33.33%)	0/13 (0.00%)	0/12 (0.00%)	0/4 (0.00%)
Reproductive system and breast disorders
Balanoposthitis † 1	0/3 (0.00%)	0/13 (0.00%)	0/12 (0.00%)	1/4 (25.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/3 (0.00%)	3/13 (23.08%)	7/12 (58.33%)	1/4 (25.00%)
Nasal congestion † 1	1/3 (33.33%)	2/13 (15.38%)	2/12 (16.67%)	0/4 (0.00%)
Rhinorrhoea † 1	0/3 (0.00%)	2/13 (15.38%)	2/12 (16.67%)	1/4 (25.00%)
Upper respiratory tract congestion † 1	0/3 (0.00%)	2/13 (15.38%)	1/12 (8.33%)	0/4 (0.00%)
Respiration abnormal † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Sleep apnoea syndrome † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Atelectasis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Choking † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Hypoxia † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Respiratory tract congestion † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Rhonchi † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	1/3 (33.33%)	2/13 (15.38%)	3/12 (25.00%)	0/4 (0.00%)
Dermatitis diaper † 1	1/3 (33.33%)	2/13 (15.38%)	0/12 (0.00%)	1/4 (25.00%)
Eczema † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Erythema † 1	0/3 (0.00%)	1/13 (7.69%)	1/12 (8.33%)	0/4 (0.00%)
Alopecia † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Blister † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Dermatitis contact † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Dry skin † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Hair growth abnormal † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Papule † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Perioral dermatitis † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Skin irritation † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Urticaria † 1	0/3 (0.00%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Vascular disorders
Hypertension † 1	0/3 (0.00%)	3/13 (23.08%)	0/12 (0.00%)	0/4 (0.00%)
Hypotension † 1	1/3 (33.33%)	0/13 (0.00%)	1/12 (8.33%)	0/4 (0.00%)
Aortic dilatation † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
Flushing † 1	0/3 (0.00%)	1/13 (7.69%)	0/12 (0.00%)	0/4 (0.00%)
1 Term from vocabulary, MedDRA (23.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

A comparison of the results from this study to the results from the natural history observational study (Pediatric Neuromuscular Clinical Research Network (PNCR), Finkel et al, 2014) are included in the Novartis Clinical Trial Results, as a historical control. These full results are available via this link: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17933

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

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

Publications:

Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, Schmelzer L, Meyer K, Kolb SJ, Schumperli D, Kaspar BK, Burghes AH. A large animal model of spinal muscular atrophy and correction of phenotype. Ann Neurol. 2015 Mar;77(3):399-414. doi: 10.1002/ana.24332. Epub 2015 Feb 9.

Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.

Retraction in: Nat Biotechnol. 2022 Nov;40(11):1692

Meyer K, Ferraiuolo L, Schmelzer L, Braun L, McGovern V, Likhite S, Michels O, Govoni A, Fitzgerald J, Morales P, Foust KD, Mendell JR, Burghes AH, Kaspar BK. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015 Mar;23(3):477-87. doi: 10.1038/mt.2014.210. Epub 2014 Oct 31.

• Responsible Party: Novartis ( Novartis Gene Therapies )
• ClinicalTrials.gov Identifier: NCT03381729
• Other Study ID Numbers: AVXS-101-CL-102; 2020-003678-28 ( EudraCT Number ); COAV101A12102 ( Other Identifier: Novartis )
• First Submitted: December 13, 2017
• First Posted: December 22, 2017
• Results First Submitted: May 18, 2022
• Results First Posted: February 16, 2023
• Last Update Posted: April 24, 2023