Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration - Sorbonne Université
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
  • Function : Author
Jamie L Fraser
  • Function : Author
Neal Hermanowicz
  • Function : Author
Robert Jech
Hyder A Jinnah
  • Function : Author
Tomasz Kmiec
  • Function : Author
Anthony Lang
  • Function : Author
Maria J Martí
  • Function : Author
Saadet Mercimek-Andrews
  • Function : Author
Migvis Monduy
  • Function : Author
Graeme A.M. Nimmo
  • Function : Author
Belen Perez-Dueñas
  • Function : Author
Lluis Planellas
  • Function : Author
Nivedita Thakur
  • Function : Author
Laura Tochen
  • Function : Author
Nora Vanegas-Arroyave
  • Function : Author
Giovanna Zorzi
  • Function : Author
Colleen Burns
  • Function : Author
Feriandas Greblikas
  • Function : Author

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.
Fichier principal
Vignette du fichier
Movement Disorders - 2020 - Klopstock - Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase Associated.pdf (298.19 Ko) Télécharger le fichier
Origin Publication funded by an institution
Licence

Dates and versions

hal-04514856 , version 1 (21-03-2024)

Licence

Identifiers

Cite

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⟩
9 View
9 Download

Altmetric

Share

More