Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy
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.
Timeline
- Start
- 2017-12-14
- Primary completion
- 2021-11-18
- Completion
- 2021-11-18
Outcome
Mixed primary results
Stopped (Business): “Based upon overall strategic objectives within the broader intrathecal clinical development program, Novartis Gene Therapies decided to terminate the study early.”
registry analysis (superiority test); Cohort 2: 1.2E14 vg - Age 6 to <24 Months; p >0.9999; Difference in Percent -6.0 (95% CI -21.8 to 22.8); Fisher Exact NCT03381729 ↗
registry analysis (superiority test); Cohort 2: 1.2E14 vg - Age 24 to <60 Months; p = 0.0027; Difference Between Least Squares Mean 5.5 (95% CI 1.9 to 9.0); Mixed-Model Repeat Measure NCT03381729 ↗
Publications
- Background Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, Schmelzer L, Meyer K, Kolb SJ, Schumperli D, Kaspar BK, Burghes AH. A large animal model of spinal muscular atrophy and correction of phenotype. Ann Neurol. 2015 Mar;77(3):399-414. doi: 10.1002/ana.24332. Epub 2015 Feb 9.
- Background Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.
- Background Meyer K, Ferraiuolo L, Schmelzer L, Braun L, McGovern V, Likhite S, Michels O, Govoni A, Fitzgerald J, Morales P, Foust KD, Mendell JR, Burghes AH, Kaspar BK. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015 Mar;23(3):477-87. doi: 10.1038/mt.2014.210. Epub 2014 Oct 31.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Onasemnogene Abeparvovec-xioi | Gene therapy (AAV / viral vector) | 6e+13 vg | Intrathecal |
| Subject | Onasemnogene Abeparvovec-xioi | Gene therapy (AAV / viral vector) | 1.2e+14 vg | Intrathecal |
| Subject | Onasemnogene Abeparvovec-xioi | Gene therapy (AAV / viral vector) | 2.4e+14 vg | Intrathecal |