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A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α‐synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates co...

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Autores principales: Meissner, Wassilios G., Traon, Anne Pavy‐Le, Foubert‐Samier, Alexandra, Galabova, Gergana, Galitzky, Monique, Kutzelnigg, Alexandra, Laurens, Brice, Lührs, Petra, Medori, Rossella, Péran, Patrice, Sabatini, Umberto, Vergnet, Sylvain, Volc, Dieter, Poewe, Werner, Schneeberger, Achim, Staffler, Günther, Rascol, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754431/
https://www.ncbi.nlm.nih.gov/pubmed/32882100
http://dx.doi.org/10.1002/mds.28218
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author Meissner, Wassilios G.
Traon, Anne Pavy‐Le
Foubert‐Samier, Alexandra
Galabova, Gergana
Galitzky, Monique
Kutzelnigg, Alexandra
Laurens, Brice
Lührs, Petra
Medori, Rossella
Péran, Patrice
Sabatini, Umberto
Vergnet, Sylvain
Volc, Dieter
Poewe, Werner
Schneeberger, Achim
Staffler, Günther
Rascol, Olivier
author_facet Meissner, Wassilios G.
Traon, Anne Pavy‐Le
Foubert‐Samier, Alexandra
Galabova, Gergana
Galitzky, Monique
Kutzelnigg, Alexandra
Laurens, Brice
Lührs, Petra
Medori, Rossella
Péran, Patrice
Sabatini, Umberto
Vergnet, Sylvain
Volc, Dieter
Poewe, Werner
Schneeberger, Achim
Staffler, Günther
Rascol, Olivier
author_sort Meissner, Wassilios G.
collection PubMed
description Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α‐synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that are designed to induce a sustained antibody response, specifically targeting pathogenic assemblies of α‐synuclein. The objectives of the current study were to evaluate primarily the safety and tolerability of PD01A and PD03A in patients with early MSA. Thirty patients (11 women) were randomized to receive 5 subcutaneous injections of either PD01A (n = 12), PD03A (n = 12), or placebo (n = 6) in this patient‐ and examiner‐blinded, placebo‐controlled, 52‐week phase 1 clinical trial (ClinicalTrial.gov identifier: NCT02270489). Immunogenicity and clinical scores were assessed as secondary objectives. Twenty‐nine patients reported a total of 595 treatment‐emergent adverse events (mild or moderate, n = 555; severe, n = 40). Treatment‐related adverse events included 190 injection‐site reactions typically observed in vaccination trials with similar per‐subject incidence in the treatment groups over time. Sustained IgG titers were observed in the PD01A‐treated group, and 89% of treated patients developed a PD01‐specific antibody response after receiving all injections. Induced antibodies displayed clear reactivity to the α‐synuclein target epitope. Titers and antibody responder rate (58%) were lower in the PD03A‐treated group. In conclusion, both PD01A and PD03A were safe and well tolerated. PD01A triggered a rapid and long‐lasting antibody response that specifically targeted the α‐synuclein epitope. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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spelling pubmed-77544312020-12-28 A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy Meissner, Wassilios G. Traon, Anne Pavy‐Le Foubert‐Samier, Alexandra Galabova, Gergana Galitzky, Monique Kutzelnigg, Alexandra Laurens, Brice Lührs, Petra Medori, Rossella Péran, Patrice Sabatini, Umberto Vergnet, Sylvain Volc, Dieter Poewe, Werner Schneeberger, Achim Staffler, Günther Rascol, Olivier Mov Disord Regular Issue Articles Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α‐synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that are designed to induce a sustained antibody response, specifically targeting pathogenic assemblies of α‐synuclein. The objectives of the current study were to evaluate primarily the safety and tolerability of PD01A and PD03A in patients with early MSA. Thirty patients (11 women) were randomized to receive 5 subcutaneous injections of either PD01A (n = 12), PD03A (n = 12), or placebo (n = 6) in this patient‐ and examiner‐blinded, placebo‐controlled, 52‐week phase 1 clinical trial (ClinicalTrial.gov identifier: NCT02270489). Immunogenicity and clinical scores were assessed as secondary objectives. Twenty‐nine patients reported a total of 595 treatment‐emergent adverse events (mild or moderate, n = 555; severe, n = 40). Treatment‐related adverse events included 190 injection‐site reactions typically observed in vaccination trials with similar per‐subject incidence in the treatment groups over time. Sustained IgG titers were observed in the PD01A‐treated group, and 89% of treated patients developed a PD01‐specific antibody response after receiving all injections. Induced antibodies displayed clear reactivity to the α‐synuclein target epitope. Titers and antibody responder rate (58%) were lower in the PD03A‐treated group. In conclusion, both PD01A and PD03A were safe and well tolerated. PD01A triggered a rapid and long‐lasting antibody response that specifically targeted the α‐synuclein epitope. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. John Wiley & Sons, Inc. 2020-09-03 2020-11 /pmc/articles/PMC7754431/ /pubmed/32882100 http://dx.doi.org/10.1002/mds.28218 Text en © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Regular Issue Articles
Meissner, Wassilios G.
Traon, Anne Pavy‐Le
Foubert‐Samier, Alexandra
Galabova, Gergana
Galitzky, Monique
Kutzelnigg, Alexandra
Laurens, Brice
Lührs, Petra
Medori, Rossella
Péran, Patrice
Sabatini, Umberto
Vergnet, Sylvain
Volc, Dieter
Poewe, Werner
Schneeberger, Achim
Staffler, Günther
Rascol, Olivier
A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title_full A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title_fullStr A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title_full_unstemmed A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title_short A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy
title_sort phase 1 randomized trial of specific active α‐synuclein immunotherapies pd01a and pd03a in multiple system atrophy
topic Regular Issue Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754431/
https://www.ncbi.nlm.nih.gov/pubmed/32882100
http://dx.doi.org/10.1002/mds.28218
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