Back to resultsLong-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
Primary Purpose
Spinal Muscular Atrophy (SMA)
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
onasemnogene abeparvovec
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Muscular Atrophy (SMA) 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, Spinal Muscular Atrophy (SMA), survival motor neuron 1 gene (SMN1), SMN protein depletion, survival motor neuron 2 gene (SMN2), chromosome 5q13, neurogenetic disorder, onasemnogene abeparvovec
Eligibility Criteria
Inclusion Criteria:
- Participated in an OAV101 clinical trial.
- Written informed consent must be obtained before any assessment is performed.
- Patient/Parent/legal guardian willing and able to comply with study procedures.
Exclusion Criteria:
There are no exclusion criteria for this study.
Sites / Locations
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec
Arm Description
Patients who received OAV101 IT or OAV101 IV in AveXis/ Novartis or Novartis Gene Therapies Phase I to IIIb clinical trials
Outcomes
Primary Outcome Measures
Number of participants with treatment-emergent serious adverse events (SAEs)
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria:
fatal
life-threatening
results in persistent or significant disability/incapacity
constitutes a congenital anomaly/birth defect, fetal death or congenital abnormality or birth defect
requires in-patient hospitalization or prolongation of existing hospitalization, unless hospitalization is for routine treatment or monitoring of the studied indication, not associated with any deterioration in condition
is medically significant, e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above
Number of participants with important identified and important potential risks (Adverse Events of Special Interest (AESI))
The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator.
Secondary Outcome Measures
The number of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist
The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with 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.
The number of participants demonstrating maintenance of each developmental milestone according to the Developmental Milestone Checklist
The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with 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.
Change from Baseline in the Hammersmith Functional Motor Scale - Expanded (HFMSE) total score
The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Change from Baseline in the Revised Upper Limb Module (RULM) total score
The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05335876
Brief Title
Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
Official Title
Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 IT or OAV101 IV in Clinical Trials
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2022 (Actual)
Primary Completion Date
October 18, 2039 (Anticipated)
Study Completion Date
October 18, 2039 (Anticipated)
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
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a global, prospective, multi-center study that is designed to assess the long-term safety and efficacy of OAV101 in patients who participated in an OAV101 clinical trial. The assessments of safety and efficacy in Study COAV101A12308 will continue for 15 years from the date of OAV101 administration in the parent study.
Detailed Description
The study is comprised of a Baseline Period and 3 Follow-up Periods. Follow-up Periods 1 and 2 consist of in-person visits and Period 3 consists of tele-visits. Follow-up Periods 1 and 2, which includes Baseline through Year 5 visits, assessments will be performed at the Investigational site. During Follow-up Period 3 (Year 6 to up to Year 15 after OAV101 administration), participants/caregivers will be contacted using tele-visits annually for remote assessments. All patients will enter the study at the baseline visit and continue until 15 years since OAV101 administration is reached. Total duration of participation in the study will be dependent upon time of enrollment relative to OAV101 administration and will vary by participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy (SMA)
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, Spinal Muscular Atrophy (SMA), survival motor neuron 1 gene (SMN1), SMN protein depletion, survival motor neuron 2 gene (SMN2), chromosome 5q13, neurogenetic disorder, onasemnogene abeparvovec
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
260 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec
Arm Type
Experimental
Arm Description
Patients who received OAV101 IT or OAV101 IV in AveXis/ Novartis or Novartis Gene Therapies Phase I to IIIb clinical trials
Intervention Type
Biological
Intervention Name(s)
onasemnogene abeparvovec
Other Intervention Name(s)
Zolgensma
Intervention Description
Onasemnogene abeparvovec is a non-replicating recombinant adeno-associated virus serotype 9 containing the human survival motor neuron gene under the control of the ytomegalovirus enhancer/chicken β-actin-hybrid promoter. Onasemnogene abeparvovec is administered as a one-time intravenous (IV) infusion or intrathecal (IT) injection. Dosage determined by participant weight.
Primary Outcome Measure Information:
Title
Number of participants with treatment-emergent serious adverse events (SAEs)
Description
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria:
fatal
life-threatening
results in persistent or significant disability/incapacity
constitutes a congenital anomaly/birth defect, fetal death or congenital abnormality or birth defect
requires in-patient hospitalization or prolongation of existing hospitalization, unless hospitalization is for routine treatment or monitoring of the studied indication, not associated with any deterioration in condition
is medically significant, e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above
Time Frame
Up to 15 years
Title
Number of participants with important identified and important potential risks (Adverse Events of Special Interest (AESI))
Description
The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator.
Time Frame
Up to 15 years
Secondary Outcome Measure Information:
Title
The number of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist
Description
The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with 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
5 years
Title
The number of participants demonstrating maintenance of each developmental milestone according to the Developmental Milestone Checklist
Description
The Developmental Milestone Checklist is a sponsor created list of items using relevant definitions obtained from World Health Organization Multicentre Growth Reference Study (WHO-MGRS). These will be assessed via the milestone checklist, formed of 6 yes/no questions. The developmental milestones are: sitting with 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
5 years
Title
Change from Baseline in the Hammersmith Functional Motor Scale - Expanded (HFMSE) total score
Description
The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Time Frame
5 years
Title
Change from Baseline in the Revised Upper Limb Module (RULM) total score
Description
The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
Time Frame
5 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participated in an OAV101 clinical trial.
Written informed consent must be obtained before any assessment is performed.
Patient/Parent/legal guardian willing and able to comply with study procedures.
Exclusion Criteria:
There are no exclusion criteria for this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Gene Therapies Med Info (US, Latin America, Canada)
Phone
+1-833-828-3947
Email
medinfo.gtx@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Gene Therapies Med Info (Europe, Middle East, Africa, Asia-Pacific)
Phone
+353 (1) 566-2364
Email
medinfoemea.gtx@novartis.com
Facility Information:
Facility Name
Novartis Investigative Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
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
Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
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