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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03505099




Registration number
NCT03505099
Ethics application status
Date submitted
13/04/2018
Date registered
23/04/2018
Date last updated
7/09/2022

Titles & IDs
Public title
Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi 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
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - onasemnogene abeparvovec-xioi

Experimental: onasemnogene abeparvovec-xioi - One-time intravenous infusion of onasemnogene abeparvovec-xioi at 1.1 X 10^14 vg/kg


Other interventions: onasemnogene abeparvovec-xioi
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
Cohort 1: Number of Participants Who Achieved Sitting Alone for at Least 30 Seconds
Timepoint [1] 0 0
From Day 1 up to 18 months of age visit
Primary outcome [2] 0 0
Cohort 2: Number of Participants Who Achieved Standing Alone for at Least 3 Seconds
Timepoint [2] 0 0
From Day 1 up to 24 months of age visit
Secondary outcome [1] 0 0
Cohort 1: Event-free Survival at 14 Months of Age
Timepoint [1] 0 0
From Day 1 up to 14 months of age
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
From Day 1 up to 18 months of age
Secondary outcome [3] 0 0
Cohort 2: Number of Participants Who Achieved the Ability to Walk Alone
Timepoint [3] 0 0
From Day 1 up to 24 months of age visit

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

- Parent(s)/legal guardian(s) willing and able to complete the informed consent process
and comply with study procedures and visit schedule

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

a. 2 copies of SMN2 (n =14)

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

1. 3 copies of SMN2 (n =12)
Minimum age
No limit
Maximum age
42 Days
Sex
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

- 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 abnormal laboratory values (gamma-glutamyl transferase [GGT],
Alanine transaminase [ALT], and aspartate aminotransferase [AST], or total bilirubin >
2 × the upper limit of normal [ULN], creatinine = 1.0 mg/dL, hemoglobin [Hgb] < 8 or >
18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy.
Patients with an elevated bilirubin level that is unequivocally the result of neonatal
jaundice shall not be excluded

- 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

- Biological mother with active viral infection as determined by screening laboratory
samples (includes human immunodeficiency virus [HIV] or positive serology for
hepatitis B or C)

• Biological mothers with clinical suspicion of Zika virus that meet Centers for
Disease Control and Prevention (CDC) Zika virus epidemiological criteria including
history of residence in or travel to a geographic region with active Zika transmission
at the time of travel will be tested for Zika virus RNA. Positive results warrant
confirmed negative Zika virus RNA testing in the patient prior to enrollment.

- Serious nonrespiratory tract illness requiring systemic treatment and/or
hospitalization within 2 Weeks prior to screening

- Upper or lower respiratory infection requiring medical attention, medical
intervention, or increase in supportive care of any manner within 4 Weeks prior to
dosing

- Severe nonpulmonary/respiratory tract infection within 4 Weeks before administration
of gene replacement therapy or concomitant illness that, in the opinion of the
Investigator or Sponsor medical monitor, creates unnecessary risks for gene
replacement therapy such as:

- Major renal or hepatic impairment

- Known seizure disorder

- Diabetes mellitus

- Idiopathic hypocalciuria

- Symptomatic cardiomyopathy

- Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or
their excipients

- Previous, planned or expected major surgical procedure including scoliosis repair
surgery/procedure during the study assessment period

- Concomitant use of any of the following: drugs for treatment of myopathy or
neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive
therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive
therapy within 4 Weeks prior to gene replacement therapy

- AntiAAV9 antibody titer >1:50 as determined by Enzyme-linked Immunosorbent Assay
(ELISA) binding immunoassay

• Should a potential patient demonstrate AntiAAV9 antibody titer >1:50, he or she may
receive retesting inside the 30-Day screening period and will be eligible to
participate if the AntiAAV9 antibody titer upon retesting is =1:50, provided the <6
Week age requirement at the time of dosing is still met

- Biological mother involved with the care of the child refuses anti-AAV9 antibody
testing prior to dosing

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/06/2021
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 0 0
2145 - 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
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Belgium
State/province [12] 0 0
Liège
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Japan
State/province [14] 0 0
Tokyo
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Gene Therapies
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PRA Health Sciences
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the safety and efficacy of intravenous onasemnogene abeparvovec-xioi in
pre-symptomatic patients with SMA and 2 or 3 copies SMN2
Trial website
https://clinicaltrials.gov/ct2/show/NCT03505099
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries