Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration

作者：Thomas Klopstock, Aleksandar Videnović, A. Bischoff, Cécilia Bonnet, Laura Cif, Cynthia L. Comella, Marta Correa‐Vela, Maria L. Escolar, Jamie L. Fraser, Victoria González, Neal Hermanowicz, Robert Jech, Hyder A. Jinnah, Tomasz Kmieć, Anthony E. Lang, M. J. Martí, Saadet Mercimek‐Andrews, Migvis Monduy, Graeme Nimmo, Belén Pérez‐Dueñas, Helle Cecilie Viekilde Pfeiffer, Lluís Planellás, Emmanuel Roze, Nivedita Thakur, Laura Tochen, Nora Vanegas‐Arroyave, Giovanna Zorzi, Colleen Burns, Feriandas Greblikas · 发表于：Movement Disorders · 年份：2020 · DOI：10.1002/mds.28392 · 被引用次数：28 · 研究领域：Neurological diseases and metabolism、Metalloenzymes and iron-sulfur proteins、Hereditary Neurological Disorders

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) a...