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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
Date last updated
9/10/2024

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
To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing = 8.5 kg and = 21 kg, over a 12 month period.
Trial website
https://clinicaltrials.gov/study/NCT04851873
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04851873