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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03505099




Registration number
NCT03505099
Ethics application status
Date submitted
13/04/2018
Date registered
13/04/2018
Date last updated
20/12/2018

Titles & IDs
Public title
Pre-Symptomatic Study of Intravenous AVXS-101 in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2
Scientific title
A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants With Genetically Diagnosed and Pre-symptomatic Spinal Muscular Atrophy With Multiple Copies of SMN2
Secondary ID [1] 0 0
2017-004087-35
Secondary ID [2] 0 0
AVXS-101-CL-304
Universal Trial Number (UTN)
Trial acronym
SPR1NT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AVXS-101

Experimental: AVXS-101 - One-time intravenous infusion of AVXS-101 at 1.1 X 1014 vg/kg


Other interventions: AVXS-101
A non-replicating recombinant AAV9 containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-ß-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.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants achieving functional independent sitting for at least 30 seconds at any visit - Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
Timepoint [1] 0 0
18 months
Primary outcome [2] 0 0
Percentage of participants achieving the ability to stand without support for at least 3 seconds at any visit - Participants with bi-allelic SMN1 deletions and 3 copies of SMN2
Timepoint [2] 0 0
24 months
Secondary outcome [1] 0 0
Percentage of participants surviving without permanent ventilation in the absence of acute illness and perioperatively - Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Percentage of participants achieving the ability to maintain weight at or above the 3rd percentile without non-oral/mechanical feeding support at any visit - Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
Timepoint [2] 0 0
18 months
Secondary outcome [3] 0 0
Percentage of participants demonstrating the ability to walk alone at any visit - Participants with bi-allelic SMN1 deletions and 3 copies of SMN2. Ability to walk alone is defined as the ability to take at least 5 steps independently displaying coordination and balance.
Timepoint [3] 0 0
24 months

Eligibility
Key inclusion criteria
- Age =6 weeks (=42 days) at time of dose

- Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing
test

- Compound muscle action potential (CMAP) =2mV at Baseline; centralized review of CMAP
data will be conducted

- Gestational age of 35 to 42 weeks Patients with 2 copies of SMN2 (n =15)

- Patients with pre-symptomatic SMA Type 1 as determined by the following features:

- 2 copies of SMN2 Patients with 3 copies of SMN2 (n =12)

- Patients with pre-symptomatic SMA Type 2 as determined by the following features:

- 3 copies of SMN2 Patients with 4 copies of SMN2 (n =17)

- Patients with pre-symptomatic SMA Type 3 as determined by the following features:

- 4 copies of SMN2
Minimum age
No limit
Maximum age
42 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Weight at screening visit <2 kg

- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or
respiratory support) at the screening visit or for altitudes >1000 m, oxygen
saturation <92% awake or asleep without any supplemental oxygen or respiratory support
at the screening visit

- Any clinical signs or symptoms at screening or immediately prior to dosing that are,
in the opinion of the Investigator, strongly suggestive of SMA (e.g., tongue
fasciculation, hypotonia, areflexia)

- Tracheostomy or current prophylactic use or requirement of noninvasive ventilatory
support at any time and for any duration prior to screening or during the screening
period

- Patients with signs of aspiration/inability to tolerate nonthickened liquids based on
a formal swallowing test performed as part of screening or patients receiving any
non-oral feeding method

- Clinically significant abnormalities in hematology or clinical chemistry parameters as
determined by investigator or medical monitor

- Treatment with an investigational or commercial product, including nusinersen, given
for the treatment of SMA. This includes any history of gene therapy, prior antisense
oligonucleotide treatment, or cell transplantation.

- Patients whose weight-for-age is below the third percentile based on World Health
Organization (WHO) Child Growth Standards [25]

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospitals Network and - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Belgium
State/province [14] 0 0
Liège
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Germany
State/province [16] 0 0
München
Country [17] 0 0
Israel
State/province [17] 0 0
Tel Aviv
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gyeungsangnamdo
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taipei
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AveXis, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A global study of intravenous AVXS-101 in pre-symptomatic patients with SMA with 2, 3, and 4
copies of SMN2
Trial website
https://clinicaltrials.gov/show/NCT03505099
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Doug Feltner, MD
Address 0 0
AveXis, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AveXis MedInfo
Address 0 0
Country 0 0
Phone 0 0
833-828-3947
Fax 0 0
Email 0 0
medinfo@avexis.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable