| Title: |
Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial |
| Authors: |
Shieh, PB; Kuntz, NL; Dowling, JJ; Müller-Felber, W; Bönnemann, CG; Seferian, AM; Servais, L; Smith, BK; Muntoni, F; Blaschek, A; Foley, AR; Saade, DN; Neuhaus, S; Alfano, LN; Beggs, AH; Buj-Bello, A; Childers, MK; Duong, T; Graham, RJ; Jain, M; Coats, J; MacBean, V; James, ES; Lee, J; Mavilio, F; Miller, W; Varfaj, F; Murtagh, M; Han, C; Noursalehi, M; Lawlor, MW; Prasad, S; Rico, S |
| Publisher Information: |
Elsevier |
| Publication Year: |
2023 |
| Collection: |
Brunel University London: Brunel University Research Archive (BURA) |
| Description: |
Data sharing: Researchers may request access to anonymised participant-level data, trial-level data, and protocols from clinical trials sponsored by Astellas Gene Therapies at medinfo.us@astellas.com. For the Astellas criteria on data sharing see https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx. ; Supplementary Materials are available online at: https://www.sciencedirect.com/science/article/pii/S1474442223003137#sec1 . ; Copyright © 2023 The Author(s). Background: X-linked myotubular myopathy is a rare, life-threatening, congenital muscle disease observed mostly in males, which is caused by mutations in MTM1. No therapies are approved for this disease. We aimed to assess the safety and efficacy of resamirigene bilparvovec, which is an adeno-associated viral vector serotype 8 delivering human MTM1. Methods: ASPIRO is an open-label, dose-escalation trial at seven academic medical centres in Canada, France, Germany, and the USA. We included boys younger than 5 years with X-linked myotubular myopathy who required mechanical ventilator support. The trial was initially in two parts. Part 1 was planned as a safety and dose-escalation phase in which participants were randomly allocated (2:1) to either the first dose level (1·3 × 1014 vector genomes [vg]/kg bodyweight) of resamirigene bilparvovec or delayed treatment, then, for later participants, to either a higher dose (3·5 × 1014 vg/kg bodyweight) of resamirigene bilparvovec or delayed treatment. Part 2 was intended to confirm the dose selected in part 1. Resamirigene bilparvovec was administered as a single intravenous infusion. An untreated control group comprised boys who participated in a run-in study (INCEPTUS; NCT02704273) or those in the delayed treatment cohort who did not receive any dose. The primary efficacy outcome was the change from baseline to week 24 in hours of daily ventilator support. After three unexpected deaths, dosing at the higher dose was stopped and the two-part feature of the study design was eliminated. ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
1125 - 1139; Print-Electronic |
| Language: |
English |
| Relation: |
The Lancet Neurology; https://bura.brunel.ac.uk/handle/2438/27683 |
| DOI: |
10.1016/s1474-4422(23)00313-7 |
| Availability: |
https://bura.brunel.ac.uk/handle/2438/27683; https://doi.org/10.1016/s1474-4422(23)00313-7 |
| Rights: |
Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license (https://creativecommons.org/licenses/by-nc-nd/4.0/). ; https://creativecommons.org/licenses/by-nc-nd/4.0/ ; The Author(s) |
| Accession Number: |
edsbas.36D7C0A2 |
| Database: |
BASE |