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MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study

BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 i...

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Autores principales: Tourbah, Ayman, Gout, Olivier, Vighetto, Alain, Deburghgraeve, Véronique, Pelletier, Jean, Papeix, Caroline, Lebrun-Frenay, Christine, Labauge, Pierre, Brassat, David, Toosy, Ahmed, Laplaud, David-Axel, Outteryck, Olivier, Moreau, Thibault, Debouverie, Marc, Clavelou, Pierre, Heinzlef, Olivier, De Sèze, Jérôme, Defer, Gilles, Sedel, Frédéric, Arndt, Carl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061426/
https://www.ncbi.nlm.nih.gov/pubmed/29808469
http://dx.doi.org/10.1007/s40263-018-0528-2
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author Tourbah, Ayman
Gout, Olivier
Vighetto, Alain
Deburghgraeve, Véronique
Pelletier, Jean
Papeix, Caroline
Lebrun-Frenay, Christine
Labauge, Pierre
Brassat, David
Toosy, Ahmed
Laplaud, David-Axel
Outteryck, Olivier
Moreau, Thibault
Debouverie, Marc
Clavelou, Pierre
Heinzlef, Olivier
De Sèze, Jérôme
Defer, Gilles
Sedel, Frédéric
Arndt, Carl
author_facet Tourbah, Ayman
Gout, Olivier
Vighetto, Alain
Deburghgraeve, Véronique
Pelletier, Jean
Papeix, Caroline
Lebrun-Frenay, Christine
Labauge, Pierre
Brassat, David
Toosy, Ahmed
Laplaud, David-Axel
Outteryck, Olivier
Moreau, Thibault
Debouverie, Marc
Clavelou, Pierre
Heinzlef, Olivier
De Sèze, Jérôme
Defer, Gilles
Sedel, Frédéric
Arndt, Carl
author_sort Tourbah, Ayman
collection PubMed
description BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS: The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS: Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (− 0.061 logMAR, + 3.1 letters) than with placebo (− 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (− 0.058 logMAR) with MD1003 and worsened by − 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS: MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION: EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40263-018-0528-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-60614262018-08-09 MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study Tourbah, Ayman Gout, Olivier Vighetto, Alain Deburghgraeve, Véronique Pelletier, Jean Papeix, Caroline Lebrun-Frenay, Christine Labauge, Pierre Brassat, David Toosy, Ahmed Laplaud, David-Axel Outteryck, Olivier Moreau, Thibault Debouverie, Marc Clavelou, Pierre Heinzlef, Olivier De Sèze, Jérôme Defer, Gilles Sedel, Frédéric Arndt, Carl CNS Drugs Original Research Article BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS: The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS: Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (− 0.061 logMAR, + 3.1 letters) than with placebo (− 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (− 0.058 logMAR) with MD1003 and worsened by − 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS: MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION: EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40263-018-0528-2) contains supplementary material, which is available to authorized users. Springer International Publishing 2018-05-28 2018 /pmc/articles/PMC6061426/ /pubmed/29808469 http://dx.doi.org/10.1007/s40263-018-0528-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research Article
Tourbah, Ayman
Gout, Olivier
Vighetto, Alain
Deburghgraeve, Véronique
Pelletier, Jean
Papeix, Caroline
Lebrun-Frenay, Christine
Labauge, Pierre
Brassat, David
Toosy, Ahmed
Laplaud, David-Axel
Outteryck, Olivier
Moreau, Thibault
Debouverie, Marc
Clavelou, Pierre
Heinzlef, Olivier
De Sèze, Jérôme
Defer, Gilles
Sedel, Frédéric
Arndt, Carl
MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title_full MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title_fullStr MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title_full_unstemmed MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title_short MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study
title_sort md1003 (high-dose pharmaceutical-grade biotin) for the treatment of chronic visual loss related to optic neuritis in multiple sclerosis: a randomized, double-blind, placebo-controlled study
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061426/
https://www.ncbi.nlm.nih.gov/pubmed/29808469
http://dx.doi.org/10.1007/s40263-018-0528-2
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