Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04851873
Registration number
NCT04851873
Ethics application status
Date submitted
6/04/2021
Date registered
21/04/2021
Date last updated
5/01/2024
Titles & IDs
Public title
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
Query!
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)
Query!
Secondary ID [1]
0
0
2020-005995-37
Query!
Secondary ID [2]
0
0
COAV101A12306
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
SMART
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy
0
0
Query!
Condition category
Condition code
Musculoskeletal
0
0
0
0
Query!
Other muscular and skeletal disorders
Query!
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Other
0
0
0
0
Query!
Research that is not of generic health relevance and not applicable to specific health categories listed above
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Other interventions - OAV101
Experimental: OAV101 - Participants received a single IV dose administration of OAV101
Other interventions: OAV101
Gene Therapy - 1.1e14 vector genome (vg)/kg as a one-time IV infusion was administered over approximately 60 minutes.
Query!
Intervention code [1]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Up to Month 12
Query!
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
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Up to Month 12
Query!
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
Query!
Assessment method [3]
0
0
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).
Query!
Timepoint [3]
0
0
12 months
Query!
Primary outcome [4]
0
0
Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
Primary outcome [5]
0
0
Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
Primary outcome [6]
0
0
Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)
Query!
Assessment method [6]
0
0
Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)
Query!
Timepoint [6]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
Primary outcome [7]
0
0
Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)
Query!
Assessment method [7]
0
0
Change from baseline in vital signs measurements - Pulse Rate (beats/min
Query!
Timepoint [7]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
Primary outcome [8]
0
0
Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature
Query!
Assessment method [8]
0
0
Change from baseline in vital signs measurements - temperature (degrees Celsius)
Temperature-Low:<=35ºC(Any Age),High:>=38.4ºC(<18 yrs).
Query!
Timepoint [8]
0
0
12 months
Query!
Primary outcome [9]
0
0
Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)
Query!
Assessment method [9]
0
0
Query!
Timepoint [9]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
Primary outcome [10]
0
0
Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level
Query!
Assessment method [10]
0
0
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.
Query!
Timepoint [10]
0
0
Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52
Query!
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.
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Baseline, Week 26 and Week 52
Query!
Secondary outcome [2]
0
0
Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
Query!
Secondary outcome [3]
0
0
Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52
Query!
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
Query!
Minimum age
No limit
Query!
Query!
Maximum age
17
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
N/A
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
8/09/2021
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
13/06/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
24
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Randwick
Query!
Recruitment postcode(s) [1]
0
0
2031 - Randwick
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Massachusetts
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Missouri
Query!
Country [3]
0
0
Belgium
Query!
State/province [3]
0
0
Leuven
Query!
Country [4]
0
0
Canada
Query!
State/province [4]
0
0
Quebec
Query!
Country [5]
0
0
France
Query!
State/province [5]
0
0
Garches
Query!
Country [6]
0
0
France
Query!
State/province [6]
0
0
Strasbourg
Query!
Country [7]
0
0
Italy
Query!
State/province [7]
0
0
RM
Query!
Country [8]
0
0
Portugal
Query!
State/province [8]
0
0
Lisboa
Query!
Country [9]
0
0
Taiwan
Query!
State/province [9]
0
0
Kaohsiung
Query!
Country [10]
0
0
Taiwan
Query!
State/province [10]
0
0
Taipei
Query!
Country [11]
0
0
United Kingdom
Query!
State/province [11]
0
0
London
Query!
Country [12]
0
0
United Kingdom
Query!
State/province [12]
0
0
Newcastle Upon Tyne
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04851873
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04851873
Download to PDF