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Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1

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ClinicalTrials.gov Identifier: NCT02122952
Recruitment Status : Completed
First Posted : April 25, 2014
Results First Posted : May 10, 2019
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
AveXis, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Spinal Muscular Atrophy 1
Intervention Biological: AVXS-101
Enrollment 15
Recruitment Details Recruitment period May 2014 - Dec 2015
Pre-assignment Details 30 day screening period prior to enrollment and dosing.
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Period Title: Overall Study
Started 3 12
Completed 3 12
Not Completed 0 0
Arm/Group Title Cohort 1 Cohort 2 Total
Hide Arm/Group Description

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Total of all reporting groups
Overall Number of Baseline Participants 3 12 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
<=18 years
3
 100.0%
12
 100.0%
15
 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%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 3 participants 12 participants 15 participants
6.33  (0.751) 3.42  (2.063) 4.00  (2.209)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
Female
2
  66.7%
7
  58.3%
9
  60.0%
Male
1
  33.3%
5
  41.7%
6
  40.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
Not Hispanic or Latino
3
 100.0%
10
  83.3%
13
  86.7%
Hispanic or Latino
0
   0.0%
2
  16.7%
2
  13.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 12 participants 15 participants
3 12 15
SMN2 copy number = 2  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
3
 100.0%
12
 100.0%
15
 100.0%
bi-allelic deletions of SMN1  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
3
 100.0%
12
 100.0%
15
 100.0%
Exon 7 gene modifier mutation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 12 participants 15 participants
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants That Experienced One Grade III or Higher Unanticipated, Treatment-related Toxicity That Presents With Clinical Symptoms and Requires Medical Treatment
Hide Description [Not Specified]
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Overall Number of Participants Analyzed 3 12
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
3
  25.0%
2.Secondary Outcome
Title Number of Participants Who Experienced (a) Requirement of ≥16-hour Respiratory Assistance Per Day Continuously for ≥2 Weeks in the Absence of an Acute Reversible Illness, Excluding Perioperative Ventilation, or (b) Death
Hide Description Respiratory assistance included non-invasive ventilatory support.
Time Frame 24 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Overall Number of Participants Analyzed 3 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
3.Secondary Outcome
Title Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
Hide Description CHOP-INTEND scores at baseline and 24 months post-dose. Scores = 0-64, where 64 is the maximum possible score. A higher score is indicative of higher/better motor function.
Time Frame Baseline and 24 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all treated participants with non-missing data. For a major, systemic, and externally imposed limitation of movement that prevented accurate assessment of multiple items, the total score was regarded as missing. Also, CHOP-INTEND assessments were discontinued once participants achieved higher functioning status (2 consecutive scores ≥62).
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Overall Number of Participants Analyzed 3 12
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 3 participants 12 participants
16.3  (10.50) 28.2  (12.29)
24 Months Number Analyzed 0 participants 6 participants
55.5  (1.76)
4.Other Pre-specified Outcome
Title Number of Participants With Assessed Improvement in Motor Function
Hide Description Improvement in motor function was determined by achievement of developmental milestones, specifically achievement of ability to sit unassisted for at least 30 seconds, determined by physical therapist and confirmed by an independent central video reviewer. Achievement of functional independent sitting was defined as the ability to maintain a sitting position independently for at least 30 seconds as confirmed per video evaluation by an expert central reviewer based on videos taken either at scheduled visits or provided by the parent/legal guardian.
Time Frame 24 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
full analysis set- all treated patients
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Overall Number of Participants Analyzed 3 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
9
  75.0%
Time Frame 24 months post-dose
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description

6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)

AVXS-101: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

All-Cause Mortality
Cohort 1 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/12 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 Cohort 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      10/12 (83.33%)    
Cardiac disorders     
tachycardia * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders     
gastroenteritis * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
pneumonia * 1  0/3 (0.00%)  0 7/12 (58.33%)  10
rhinovirus infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  5
enterovirus infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  3
parainfluenzae virus infection * 1  1/3 (33.33%)  1 2/12 (16.67%)  2
respiratory syncytial virus bronchiolitis * 1  1/3 (33.33%)  1 2/12 (16.67%)  2
upper respiratory tract infection * 1  0/3 (0.00%)  0 3/12 (25.00%)  3
adenovirus infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
lower respiratory tract infection * 1  0/3 (0.00%)  0 1/12 (8.33%)  2
postoperative wound infection * 1  0/3 (0.00%)  0 1/12 (8.33%)  2
bronchitis * 1  1/3 (33.33%)  1 0/12 (0.00%)  0
enterovirus test positive * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
gastroenteritis viral * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
influenza * 1  1/3 (33.33%)  1 0/12 (0.00%)  0
pneumonia parainfluenzae viral * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
pneumonia viral * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
viral upper respiratory tract infection * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Injury, poisoning and procedural complications     
femur fracture * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
post procedural hemorrhage * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Investigations     
human rhinovirus test positive * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
transaminases increased * 1  1/3 (33.33%)  1 1/12 (8.33%)  1
norovirus test positive * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
oxygen saturation decreased * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Metabolism and nutrition disorders     
dehydration * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders     
penumonia aspiration * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
respiratory distress * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
atelectasis * 1  0/3 (0.00%)  0 1/12 (8.33%)  1
respiratory failure * 1  1/3 (33.33%)  1 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 Cohort 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      12/12 (100.00%)    
Gastrointestinal disorders     
constipation * 1  1/3 (33.33%)  1 6/12 (50.00%)  8
diarrhea * 1  0/3 (0.00%)  0 3/12 (25.00%)  3
gastroesophageal reflux disease * 1  1/3 (33.33%)  1 5/12 (41.67%)  6
vomiting * 1  0/3 (0.00%)  0 8/12 (66.67%)  11
General disorders     
pyrexia * 1  1/3 (33.33%)  1 7/12 (58.33%)  12
Infections and infestations     
bronchiolitis * 1  0/3 (0.00%)  0 3/12 (25.00%)  3
conjunctivitis * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
ear infection * 1  1/3 (33.33%)  1 2/12 (16.67%)  2
enterovirus infection * 1  1/3 (33.33%)  1 3/12 (25.00%)  4
gastroenteritis viral * 1  0/3 (0.00%)  0 5/12 (41.67%)  5
otitis media * 1  2/3 (66.67%)  6 2/12 (16.67%)  3
parainfluenzae virus infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
pharyngitis streptococcal * 1  1/3 (33.33%)  1 2/12 (16.67%)  2
pneumonia * 1  0/3 (0.00%)  0 4/12 (33.33%)  4
rhinovirus infection * 1  1/3 (33.33%)  1 4/12 (33.33%)  5
upper respiratory tract infection * 1  1/3 (33.33%)  3 9/12 (75.00%)  25
urinary tract infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
viral upper respiratory tract infection * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
Injury, poisoning and procedural complications     
fall * 1  0/3 (0.00%)  0 3/12 (25.00%)  3
Investigations     
human rhinovirus test positive * 1  0/3 (0.00%)  0 3/12 (25.00%)  4
transaminases increased * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
Respiratory, thoracic and mediastinal disorders     
atelectasis * 1  0/3 (0.00%)  0 3/12 (25.00%)  3
cough * 1  0/3 (0.00%)  0 5/12 (41.67%)  11
nasal congestion * 1  0/3 (0.00%)  0 6/12 (50.00%)  9
respiratory failure * 1  0/3 (0.00%)  0 3/12 (25.00%)  5
rhinorrhoea * 1  0/3 (0.00%)  0 3/12 (25.00%)  4
wheezing * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
Skin and subcutaneous tissue disorders     
decubitus ulcer * 1  0/3 (0.00%)  0 2/12 (16.67%)  2
erythema * 1  1/3 (33.33%)  1 1/12 (8.33%)  1
rash * 1  0/3 (0.00%)  0 5/12 (41.67%)  6
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
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.
PI will provide proposed publication or presentation for review 60 days prior; Sponsor informs PI in writing of revisions required to protect Sponsor’s confidential and proprietary technical information and to address inaccurate data or inappropriate interpretations. At expiration of such 60 days, PI may proceed unless Sponsor has notified in writing that such proposed publication or presentation discloses the Sponsor’s confidential and proprietary technical information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Doug Feltner, MD
Organization: AveXis, Inc.
Phone: 833-828-3947
EMail: medinfo@avexis.com
Layout table for additonal information
Responsible Party: AveXis, Inc.
ClinicalTrials.gov Identifier: NCT02122952     History of Changes
Other Study ID Numbers: AVXS-101-CL-101
First Submitted: April 23, 2014
First Posted: April 25, 2014
Results First Submitted: July 20, 2018
Results First Posted: May 10, 2019
Last Update Posted: May 10, 2019