Ignite Creation Date:
2024-05-06 @ 10:56 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03381729
Status:
TERMINATED
Last Update Posted:
2023-04-24
First Post:
2017-12-13
Brief Title:
Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy
Sponsor:
Novartis Gene Therapies
Organization:
Novartis
Study Overview
Official Title:
Phase I Open-Label Dose Comparison Study of AVXS-101 for Sitting But Non-ambulatory Patients With Spinal Muscular Atrophy
Status:
TERMINATED
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Based upon overall strategic objectives within the broader intrathecal clinical development program Novartis Gene Therapies decided to terminate the study early
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STRONG
Brief Summary:
The purpose of this trial is to evaluate the safety and tolerability of intrathecal administration of onasemnogene abeparvovec-xioi in infants and children with Spinal Muscular Atrophy with 3 copies of SMN2 and deletion of SMN1
Detailed Description:
This is a Phase 1 single-dose administration study of infants and children with a genetic diagnosis consistent with spinal muscular atrophy SMA bi-allelic deletion of survival motor neuron 1 gene SMN1 and 3 copies of survival motor neuron 2 gene SMN2 without the genetic modifier who are able to sit but cannot stand or walk at the time of study entry Patients will receive onasemnogene abeparvovec-xioi in a dose comparison safety study of two or three potential therapeutic doses Patients will be stratified in two groups those 6 months and 24 months of age at time of dosing and those 24 months and 60 months of age at time of dosing At least 15 patients 6 months and 24 months and at least 12 patients 24 60 months will be enrolled
The first cohort will enroll three patients Cohort 1 6 months and 24 months of age who will receive administration of 60 1013 vg of onasemnogene abeparvovec-xioi Dose A There will be at least a four week interval between the dosing of each patient within the cohort Novartis Gene Therapies Inc will confer with the Data Safety Monitoring Board DSMB on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly probably or definitely related to the study agent before continuing enrollment Safety data will be reviewed by the DSMB during quarterly meetings following enrollment of the three patients and based upon the available safety data a decision will be made whether to a stop due to toxicity or b proceed to Cohort 2 using Dose B
Should the determination be made to advance to Dose B three patients 60 months of age will be enrolled Cohort 2 and will receive administration of 12 1014 vg of onasemnogene abeparvovec-xioi Dose B Again there will be at least a four-week interval between dosing of the three patients within the cohort Based on the available safety data from the three Cohort 2 patients and all of the Cohort 1 patients the DSMB will decide and document during quarterly meetings whether further four-week intervals between patients dosing is necessary Novartis Gene Therapies Inc will take this recommendation into consideration and will make the final determination whether to persist with four-week intervals between patients dosing going forward the decision will be communicated to sites and Institutional Review Boards IRBs in a formal sponsor letter Novartis Gene Therapies Inc will confer with the DSMB on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly probably or definitely related to the study agent before continuing enrollment Safety data will be reviewed by the DSMB during quarterly meetings following enrollment of the first six patients and based upon available safety data a decision will be made whether to a stop due to toxicity or b continue to enroll an additional 21 patients until there are a total of 12 patients 6 months and 24 months and 12 patients 24 and 60 months that have all received Dose B
Based upon an ongoing assessment of safety and efficacy data from patients treated with the 12 1014 vg dose an option for testing of a third dose Dose C will be considered If based on all available data this is judged to be safe and necessary three patients 60 months of age will receive Dose C 24 1014 vg administered IT A meeting of the DSMB will be called to obtain a recommendation on the safety of escalating to a higher dose prior to proceeding If a decision is made to proceed to testing a higher dose there will again be a four-week interval between dosing of the first three patients receiving Dose C as in Cohorts 1 and 2 Safety data will be reviewed by the DSMB during quarterly meetings Following enrollment of the first three Dose C patients and based upon available safety data the DSMB will be consulted and a decision will be made whether to a stop dosing Dose C due to safety concerns or b continue to enroll an additional 21 patients until there are a total of 12 patients 6 months and 24 months and 12 patients 24 and 60 months that have received Dose C
Patients from Cohort 3 will be followed for a total of 15 months post-dose The primary analyses for efficacy will be assessed when all patients reach 12 months post-dose and the primary analyses for safety will be assessed when the last patient of Cohort 3 reaches 15 months post-dose and database lock will be performed after the last patient reaches 15 months post-dose
The first cohort will enroll three patients Cohort 1 6 months and 24 months of age who will receive administration of 60 1013 vg of onasemnogene abeparvovec-xioi Dose A There will be at least a four week interval between the dosing of each patient within the cohort Novartis Gene Therapies Inc will confer with the Data Safety Monitoring Board DSMB on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly probably or definitely related to the study agent before continuing enrollment Safety data will be reviewed by the DSMB during quarterly meetings following enrollment of the three patients and based upon the available safety data a decision will be made whether to a stop due to toxicity or b proceed to Cohort 2 using Dose B
Should the determination be made to advance to Dose B three patients 60 months of age will be enrolled Cohort 2 and will receive administration of 12 1014 vg of onasemnogene abeparvovec-xioi Dose B Again there will be at least a four-week interval between dosing of the three patients within the cohort Based on the available safety data from the three Cohort 2 patients and all of the Cohort 1 patients the DSMB will decide and document during quarterly meetings whether further four-week intervals between patients dosing is necessary Novartis Gene Therapies Inc will take this recommendation into consideration and will make the final determination whether to persist with four-week intervals between patients dosing going forward the decision will be communicated to sites and Institutional Review Boards IRBs in a formal sponsor letter Novartis Gene Therapies Inc will confer with the DSMB on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly probably or definitely related to the study agent before continuing enrollment Safety data will be reviewed by the DSMB during quarterly meetings following enrollment of the first six patients and based upon available safety data a decision will be made whether to a stop due to toxicity or b continue to enroll an additional 21 patients until there are a total of 12 patients 6 months and 24 months and 12 patients 24 and 60 months that have all received Dose B
Based upon an ongoing assessment of safety and efficacy data from patients treated with the 12 1014 vg dose an option for testing of a third dose Dose C will be considered If based on all available data this is judged to be safe and necessary three patients 60 months of age will receive Dose C 24 1014 vg administered IT A meeting of the DSMB will be called to obtain a recommendation on the safety of escalating to a higher dose prior to proceeding If a decision is made to proceed to testing a higher dose there will again be a four-week interval between dosing of the first three patients receiving Dose C as in Cohorts 1 and 2 Safety data will be reviewed by the DSMB during quarterly meetings Following enrollment of the first three Dose C patients and based upon available safety data the DSMB will be consulted and a decision will be made whether to a stop dosing Dose C due to safety concerns or b continue to enroll an additional 21 patients until there are a total of 12 patients 6 months and 24 months and 12 patients 24 and 60 months that have received Dose C
Patients from Cohort 3 will be followed for a total of 15 months post-dose The primary analyses for efficacy will be assessed when all patients reach 12 months post-dose and the primary analyses for safety will be assessed when the last patient of Cohort 3 reaches 15 months post-dose and database lock will be performed after the last patient reaches 15 months post-dose
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| COAV101A12102 | OTHER | Novartis | None |
| 2020-003678-28 | EUDRACT_NUMBER | None | None |