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DC Field | Value | Language |
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dc.contributor.author | Mora, Jesús S. | - |
dc.contributor.author | Genge, Angela | - |
dc.contributor.author | Chio, Adriano | - |
dc.contributor.author | Estol, Conrado J. | - |
dc.contributor.author | Chaverri, Delia | - |
dc.contributor.author | Hernández, María | - |
dc.contributor.author | Marín, Saúl | - |
dc.contributor.author | Mascias, Javier | - |
dc.contributor.author | Rodríguez, Gabriel E. | - |
dc.contributor.author | Povedano, Mònica | - |
dc.contributor.author | Paipa, Andres Julian | - |
dc.contributor.author | Domínguez, Raúl | - |
dc.contributor.author | Gamez, Josep | - |
dc.contributor.author | Salvado, Maria | - |
dc.contributor.author | Lunetta, Christian | - |
dc.contributor.author | Ballario, Carlos | - |
dc.contributor.author | Riva, Nilo | - |
dc.contributor.author | Mandrioli, Jessica | - |
dc.contributor.author | Moussy, Alain | - |
dc.contributor.author | Kinet, Jean-Pierre | - |
dc.contributor.author | Auclair, Christian | - |
dc.contributor.author | Dubreuil, Patrice | - |
dc.contributor.author | Arnold, Vincent | - |
dc.contributor.author | Mansfield, Colin D. | - |
dc.contributor.author | Hermine, Olivier | - |
dc.contributor.author | The Ab10015 Study Group | - |
dc.date.accessioned | 2020-06-09T10:17:55Z | - |
dc.date.available | 2020-06-09T10:17:55Z | - |
dc.date.issued | 2019-07-07 | - |
dc.identifier.uri | http://hdl.handle.net/2445/164895 | - |
dc.description.abstract | Objective: To assess masitinib in the treatment of ALS. Methods: Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 mg/kg/d. Following a blinded transition from phase 2 to phase 2/3, a prospectively defined two-tiered design was implemented based on ALSFRS-R progression rate from disease-onset to baseline (ΔFS). This approach selects a more homogeneous primary efficacy population (“Normal Progressors”, ΔFS < 1.1 points/month) while concurrently permitting secondary assessment of the broader population. Primary endpoint was decline in ALSFRS-R at week-48 (ΔALSFRS-R), with the high-dose “Normal Progressor” cohort being the prospectively declared primary efficacy population. Missing data were imputed via last observation carried forward (LOCF) methodology with sensitivity analyses performed to test robustness. Results: For the primary efficacy population, masitinib (n = 99) showed significant benefit over placebo (n = 102) with a ΔALSFRS-R between-group difference (ΔLSM) of 3.4 (95% CI 0.65–6.13; p = 0.016), corresponding to a 27% slowing in rate of functional decline (LOCF methodology). Sensitivity analyses were all convergent, including the conservative multiple imputation technique of FCS-REGPMM with a ΔLSM of 3.4 (95% CI 0.53–6.33; p = 0.020). Secondary endpoints (ALSAQ-40, FVC, and time-to-event analysis) were also significant. Conversely, no significant treatment-effect according to ΔALSFRS-R was seen for the broader “Normal and Fast Progressor” masitinib 4.5 mg/kg/d cohort, or either of the low-dose (masitinib 3.0 mg/kg/d) cohorts. Rates of treatment-emergent adverse events (AEs) (regardless of causality or post-onset ΔFS) were 88% with masitinib 4.5 mg/kg/d, 85% with 3.0 mg/kg/d, and 79% with placebo. Likewise, rates of serious AE were 31, 23, and 18%, respectively. No distinct event contributed to the higher rate observed for masitinib and no deaths were related to masitinib. Conclusions: Results show that masitinib at 4.5 mg/kg/d can benefit patients with ALS. A confirmatory phase 3 study will be initiated to substantiate these data. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Informa UK Limited | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1080/21678421.2019.1632346 | - |
dc.relation.ispartof | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2020, vol. 21, issue. 1, p. 5-14 | - |
dc.relation.uri | https://doi.org/10.1080/21678421.2019.1632346 | - |
dc.rights | cc-by-nc-nd (c) Mora et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Assaigs clínics | - |
dc.subject.classification | Terapèutica | - |
dc.subject.classification | Proteïnes quinases | - |
dc.subject.other | Clinical trials | - |
dc.subject.other | Therapeutics | - |
dc.subject.other | Protein kinases | - |
dc.title | Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-06-09T06:19:08Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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Masitinib_Mora_2020.pdf | 753.12 kB | Adobe PDF | View/Open |
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