Single-Dose Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1

Summary

Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). Up to 30 patients \< 6 months (\< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

Timeline

Start

2018-08-16

Primary completion

2020-09-11

Completion

2020-09-11

Outcome

Met primary endpoint

paper 14 (44%, 97·5% CI 26-100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s PMID 34536405 ↗

paper vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001 PMID 34536405 ↗

Publications

• Mercuri E, Muntoni F, Baranello G, Masson R, Boespflug-Tanguy O, Bruno C, Corti S, Daron A, Deconinck N, Servais L, Straub V, Ouyang H, Chand D, Tauscher-Wisniewski S, Mendonca N, Lavrov A; STR1VE-EU study group. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021 Oct;20(10):832-841. doi: 10.1016/S1474-4422(21)00251-9.
• Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Onasemnogene Abeparvovec-xioi	Gene therapy (AAV / viral vector)	1.1e+14 vg/kg	Intravenous

Indications