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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)
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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)
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Secondary ID [1]
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2020-005995-37
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Secondary ID [2]
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COAV101A12306
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Universal Trial Number (UTN)
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Trial acronym
SMART
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy
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Condition category
Condition code
Musculoskeletal
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Other muscular and skeletal disorders
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Neurological
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Other neurological disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
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Assessment method [1]
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An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
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Timepoint [1]
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Up to Month 12
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Primary outcome [2]
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Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket
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Assessment method [2]
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Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy.
These were assessed by the investigator.
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Timepoint [2]
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Up to Month 12
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Primary outcome [3]
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Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure
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Assessment method [3]
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Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg).
Systolic Blood Pressure-Low:\<=5th percentile of the age(Any Age), High:\>=90th percentile of the age, gender, and height group (\<18 yrs).
Diastolic Blood Pressure-High:\>=90th percentile of the age, gender, and height group(\<18 yrs).
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Timepoint [3]
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12 months
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Primary outcome [4]
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Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)
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Assessment method [4]
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Timepoint [4]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Primary outcome [5]
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Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)
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Assessment method [5]
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Timepoint [5]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Primary outcome [6]
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Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)
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Assessment method [6]
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Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)
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Timepoint [6]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Primary outcome [7]
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Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)
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Assessment method [7]
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Change from baseline in vital signs measurements - Pulse Rate (beats/min
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Timepoint [7]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Primary outcome [8]
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Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature
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Assessment method [8]
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Change from baseline in vital signs measurements - temperature (degrees Celsius)
Temperature-Low:\<=35ºC(Any Age),High:\>=38.4ºC(\<18 yrs).
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Timepoint [8]
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12 months
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Primary outcome [9]
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Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)
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Assessment method [9]
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Timepoint [9]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Primary outcome [10]
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Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level
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Assessment method [10]
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Change from baseline in vital signs measurements - oxygen saturation level (%).
Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.
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Timepoint [10]
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Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
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Secondary outcome [1]
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Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.
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Assessment method [1]
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The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley scale of Infant and Toddler Development was modified and combined into a single scale expressly for this study, to measure developmental motor milestones. These were assessed via the milestone checklist, formed of 10 yes/no questions with optional video documentation. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
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Timepoint [1]
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Baseline, Week 26 and Week 52
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Secondary outcome [2]
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Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age
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Assessment method [2]
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The HFMSE was devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments. Each motor skill item is scored on a 3 point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher level of ability.
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Timepoint [2]
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Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
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Secondary outcome [3]
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Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.
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Assessment method [3]
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The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb preferred by the participant. The total score ranges from 0, if all the items cannot be performed, to 37, if all the activities are achieved fully without any compensation. ' Higher scores indicate higher levels of motor ability.
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Timepoint [3]
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Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
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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
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Minimum age
No limit
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Maximum age
17
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
NA
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
8/09/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
13/06/2023
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Sample size
Target
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Accrual to date
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Final
24
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Novartis Investigative Site - Randwick
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Massachusetts
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Country [2]
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United States of America
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State/province [2]
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Missouri
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Country [3]
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Belgium
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State/province [3]
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Leuven
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Country [4]
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Canada
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State/province [4]
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Quebec
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Country [5]
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France
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State/province [5]
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Garches
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Country [6]
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France
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State/province [6]
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Strasbourg
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Country [7]
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Italy
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State/province [7]
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RM
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Country [8]
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Portugal
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State/province [8]
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Lisboa
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Country [9]
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Taiwan
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State/province [9]
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Kaohsiung
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Country [10]
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Taiwan
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State/province [10]
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Taipei
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Country [11]
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United Kingdom
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State/province [11]
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London
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Country [12]
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United Kingdom
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State/province [12]
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Newcastle Upon Tyne
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT04851873
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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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/.
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/.
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What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/73/NCT04851873/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/73/NCT04851873/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04851873