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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04851873




Registration number
NCT04851873
Ethics application status
Date submitted
6/04/2021
Date registered
21/04/2021

Titles & IDs
Public title
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Scientific title
A Phase IIIb, Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Gene Replacement Therapy With Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Secondary ID [1] 0 0
2020-005995-37
Secondary ID [2] 0 0
COAV101A12306
Universal Trial Number (UTN)
Trial acronym
SMART
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
Treatment: Other - OAV101

Experimental: OAV101 - Participants received a single IV dose administration of OAV101


Treatment: Other: OAV101
Gene Therapy - 1.1e14 vector genome (vg)/kg as a one-time IV infusion was administered over approximately 60 minutes.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
Timepoint [1] 0 0
Up to Month 12
Primary outcome [2] 0 0
Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket
Timepoint [2] 0 0
Up to Month 12
Primary outcome [3] 0 0
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure
Timepoint [3] 0 0
12 months
Primary outcome [4] 0 0
Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)
Timepoint [4] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Primary outcome [5] 0 0
Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)
Timepoint [5] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Primary outcome [6] 0 0
Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)
Timepoint [6] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Primary outcome [7] 0 0
Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)
Timepoint [7] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Primary outcome [8] 0 0
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature
Timepoint [8] 0 0
12 months
Primary outcome [9] 0 0
Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)
Timepoint [9] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Primary outcome [10] 0 0
Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level
Timepoint [10] 0 0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Secondary outcome [1] 0 0
Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.
Timepoint [1] 0 0
Baseline, Week 26 and Week 52
Secondary outcome [2] 0 0
Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age
Timepoint [2] 0 0
Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
Secondary outcome [3] 0 0
Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.
Timepoint [3] 0 0
Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52

Eligibility
Key inclusion criteria
Inclusion

* Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
* Weight = 8.5 kg and = 21 kg at the time of Screening Visit 2
* Naive to treatment or have discontinued an approved drug/therapy
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion:

* Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
* BMI < 3rd percentile
* Participant with history of aspiration pneumonia or signs of aspiration
* Elevated anti-AAV9 antibody
* History of gene therapy, hematopoietic transplantation, or solid organ transplantation
* Inability to take corticosteroids
* Concomitant use of immunosuppressive therapy
* Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
* Awake hypoxemia or awake oxygen saturation level decrease
* Hepatic dysfunction
* Presence of a confirmed or suspected infection
* If previously treated with disease modifying therapy, specified washout times apply
* Documented any parental consanguinity.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
8/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/06/2023
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - 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
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
France
State/province [5] 0 0
Garches
Country [6] 0 0
France
State/province [6] 0 0
Strasbourg
Country [7] 0 0
Italy
State/province [7] 0 0
RM
Country [8] 0 0
Portugal
State/province [8] 0 0
Lisboa
Country [9] 0 0
Taiwan
State/province [9] 0 0
Kaohsiung
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taipei
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/.


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04851873