Back to resultsSafety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA) (OFELIA)
Primary Purpose
Muscular Atrophy, Spinal
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
OAV101
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Atrophy, Spinal focused on measuring Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength
Eligibility Criteria
Inclusion Criteria:
- Written informed consent/assent obtained prior to any assessment performed
- Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
- Age ≤ 24 months of age at time of treatment
3. Weight ≤17 kg at the time of Screening Period 4. Naïve to treatment or have discontinued an approved drug/therapy 5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Key Exclusion Criteria:
- Previous use of OAV101 or any AAV9 gene therapy
- Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
- Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
- Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
- Inability to take corticosteroids
- Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
- Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, ≥ ULN; CTCAE ≥ 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
- Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
- Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
OAV101
Arm Description
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
Outcomes
Primary Outcome Measures
Number of Participants with treatment emergent AEs and SAEs
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Evaluation of important identified and important potential risks
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Evaluate changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results
Clinically significant abnormal laboratory values or test results must be identified through a review of values outside of normal ranges/clinically notable ranges, significant changes from baseline or the previous visit, or values which are considered to be non-typical in participant with the underlying disease.
These will be evaluated and reported as Adverse Events if clinically significant and as applicable, per investigator assessment.
Secondary Outcome Measures
Number of participants who achieve Development Motor Milestones according to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) will used to measure developmental motor milestones. This will be assessed via the milestone checklist. The 6 developmental milestones are: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
Full Information
NCT ID
NCT05073133
First Posted
September 20, 2021
Last Updated
August 30, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05073133
Brief Title
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA)
Acronym
OFELIA
Official Title
A Phase IV Open-label, Single-arm, Single-dose, Multicenter Study to Evaluate the saFEty, toLerability and effIcacy of Gene Replacement Therapy With intravenousOAV101(AVXS101) in Pediatric Patients From Latin America With Spinal Muscular Atrophy (SMA) - OFELIA
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 4, 2021 (Actual)
Primary Completion Date
August 8, 2023 (Actual)
Study Completion Date
August 8, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene ≤ 24 months and weighing ≤ 17 kg, over a 18-month period post infusion.
Detailed Description
This is an open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of IV OAV101 in SMA participants. The study will enroll participants ≤ 24 months that weigh ≤ 17 kg. Participants will receive a single administration of IV OAV101 at the approved dose of 1.1e14 vg/kg.
Participants who meet eligibility criteria at screening and baseline visits will receive a single dose of IV OAV101 on Day 1 (Treatment period) and will be followed for a period of 18 months. The study will include a standard screening period that can last up to 20 days, during which eligibility will be assessed and baseline assessments will be performed prior to treatment.
For the study duration, participants will complete visits as defined in the Schedule of Assessments (SoA). Prednisolone treatment will be given per study protocol. On Day -1, participants will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, participants will receive a 1-time IV infusion of OAV101 and will undergo in-patient safety monitoring over the next 48 hours, after which the participant may be discharged, based on Investigator judgment.
Safety monitoring will be performed as per study schedule and protocol requirement. Safety for the participants enrolled in the study will be evaluated by the study team together with Data Monitoring Committee (DMC) as described in the charter. An interim analysis for safety and efficacy maybe performed once the last participant completes 6-months of follow-up and will include all available data up until that data cut-off. Final analysis will be planned after the 18 month visit end of study (EOS).
After study completion eligible participants will be invited to enroll into a Registry study (RESTORE) study to collect additional safety and efficacy data.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Atrophy, Spinal
Keywords
Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
OAV101 will be administered as a single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OAV101
Arm Type
Experimental
Arm Description
A single IV infusion at 1.1e14 vg/kg over approximately 60 minutes
Intervention Type
Genetic
Intervention Name(s)
OAV101
Other Intervention Name(s)
AVXS-101, Zolgensma
Intervention Description
Gene Therapy IV infusion
Primary Outcome Measure Information:
Title
Number of Participants with treatment emergent AEs and SAEs
Description
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Time Frame
18 months
Title
Evaluation of important identified and important potential risks
Description
An AE is any untoward medical occurrence (eg 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. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Time Frame
18 months
Title
Evaluate changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results
Description
Clinically significant abnormal laboratory values or test results must be identified through a review of values outside of normal ranges/clinically notable ranges, significant changes from baseline or the previous visit, or values which are considered to be non-typical in participant with the underlying disease.
These will be evaluated and reported as Adverse Events if clinically significant and as applicable, per investigator assessment.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Number of participants who achieve Development Motor Milestones according to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
Description
The World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) will used to measure developmental motor milestones. This will be assessed via the milestone checklist. The 6 developmental milestones are: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
Time Frame
6, 12 and 18 months post infusion
10. Eligibility
Sex
All
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent/assent obtained prior to any assessment performed
Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
Age ≤ 24 months of age at time of treatment
3. Weight ≤17 kg at the time of Screening Period 4. Naïve to treatment or have discontinued an approved drug/therapy 5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Key Exclusion Criteria:
Previous use of OAV101 or any AAV9 gene therapy
Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
Inability to take corticosteroids
Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, ≥ ULN; CTCAE ≥ 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
Facility Information:
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1181ACH
Country
Argentina
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1245AAM
Country
Argentina
Facility Name
Novartis Investigative Site
City
Belo Horizonte
State/Province
MG
ZIP/Postal Code
30130-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403-000
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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/.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Learn more about this trial
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA) (OFELIA)
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