Table 1. Main aspects of clinical studies with gene therapy (onasemnogene aberpavovec/AVXS-101) for SMA.
| Study/ Identifier in clinicaltrials.gov/ Date started | Phase study and Description | Target population and inclusion criteria | Sample size | Endpoints and results (when available) |
|---|---|---|---|---|
| AVXS-101-CL-101/ NCT02122952/ 2014 | Phase 1, Open-Label, two experimental arms (low and high dose) of IV single-dose AVXS-101 | SMA type 1 with two copies of SMN2 up to six or nine months age | N=15 (3 in low dose cohort and 12 in high dose cohort) | Safety and tolerability/ All patients in high dose (N=12) were event-free* and 10/12 sitting |
| START/ NCT03421977/2017 | Observational, long-term follow-up | Patients from AVXS-101-CL-101 gene replacement therapy clinical trial for SMA Type 1 | N=13 (10 patients from previous high cohort) | Long term safety data / 6/10 pt sitting, 2/10 pt standing, 2/10 pt walking in 5 years follow-up- ONGOING |
| AVXS-101-CL-303 or STR1VE-US/ NCT03306277/ 2017 | Phase 3, Open-Label, Single-Arm, of IV single-dose AVXS-101 | SMA type 1 with one or two copies of SMN2 up to 6 months of age | N=22 | 13 pt (59%) sitting for 30 sec up to 18m and 90.9% of event-free* survival |
| STR1VE-EU/ NCT03461289/ 2018 | Phase 3, Open-Label, Single-Arm, of IV single-dose AVXS-101 | SMA type 1 with one or two copies of SMN2 up to 6 months of age | N=33 | 14 pt (44%) sitting for 10 sec up to 18m / 31 pt (97%) are event-free* at 14m of age |
| SPR1NT/ NCT03505099/ 2018 | Phase 3, Open-Label, Single-Arm, of IV single-dose AVXS-101 | Pre-symptomatic patients with two or three copies of SMN2 up to 42 days (6 weeks) of live at dosing date | N=30 (cohort 1: two copies of SMN2 and cohort 2: three copies of SMN2) | All pt event-free* at 14m of age and 11/15 (79%) sitting for 30 Sec (cohort 1)/ 8/15 pt standing for 3 sec and 6/15 walking (cohort 2) |
| STRONG/ NCT03381729/2017 | Phase 1, Open-Label, dose-compared study of intrathecal single-dose AVXS-101 | SMA type 2, with three copies of SMN2, older than 6m and up to 5 years old | N=33 (3 different experimental cohorts: dose A, B and C) | ONGOING - determine optimal dose, standing ability and change in HFMSE/ walking ability and change in ventilation support |
| OFELIA/ NCT05073133/ 2021 | Phase 4, Open-label, single-arm of IV single-dose AVXS-101 | Symptomatic SMA (any type) with any copy of SMN2 up to 24m of age and Weight ≤17 kg. | N=16 | ONGOING - AEs and SAEs, changes in vital signs, cardiac safety, and laboratory results/ development of motor milestones |
*Death or continuous ventilatory support; AE: adverse events; HFMSE: Hammersmith Functional Motor Scale-Expanded; m: months; IV: intravenous; N: number; pt: patients; SAE: severe adverse events; Sec: seconds; SMA: Spinal Muscular Atrophy; SMN2: Survival Motor Neuron gene 2.