Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration - Sorbonne Université Access content directly
Journal Articles Movement Disorders Year : 2020

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration

Thomas Klopstock
  • Function : Author
  • PersonId : 1365977
Aleksandar Videnovic
  • Function : Author
Almut Turid Bischoff
  • Function : Author
Laura Cif
Cynthia Comella
  • Function : Author
Marta Correa‐vela
Maria L Escolar
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Jamie L Fraser
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Neal Hermanowicz
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Robert Jech
Hyder A Jinnah
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Tomasz Kmiec
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Anthony Lang
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Maria J Martí
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Saadet Mercimek-Andrews
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Migvis Monduy
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Graeme A.M. Nimmo
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Belen Perez-Dueñas
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Lluis Planellas
  • Function : Author
Nivedita Thakur
  • Function : Author
Laura Tochen
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Nora Vanegas-Arroyave
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Giovanna Zorzi
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Colleen Burns
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Feriandas Greblikas
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Abstract

Abstract Background Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods This randomized, double‐blind, placebo‐controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24‐week double‐blind period. Patients with pathogenic variants of PANK2 , aged 6 to 65 years, with a score ≥6 on the PKAN‐Activities of Daily Living (PKAN‐ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN‐ADL. Results Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN‐related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN‐ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment‐emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN‐ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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hal-04514856 , version 1 (21-03-2024)

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Attribution - NonCommercial

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Thomas Klopstock, Aleksandar Videnovic, Almut Turid Bischoff, Cecilia Bonnet, Laura Cif, et al.. Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration. Movement Disorders, 2020, 36 (6), pp.1342-1352. ⟨10.1002/mds.28392⟩. ⟨hal-04514856⟩
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