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Tytuł:
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Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration.
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Autorzy:
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Klopstock T; Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Munich, Germany.
Videnovic A; Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Bischoff AT; Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany.
Bonnet C; Department of Neurology, Sorbonne University, AP-HP Salpêtrière Hospital, Paris, France.
Cif L; Department of Neurosurgery, CHRU de Montpellier, Gui de Chauliac Hospital, Montpellier, France.
Comella C; Department of Neurosurgery and Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Correa-Vela M; Department of Child Neurology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Escolar ML; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Fraser JL; Rare Disease Institute, Division of Genetics and Metabolism, Children's National Medical Center, Washington, District of Columbia, USA.
Gonzalez V; Department of Neurosurgery, University Hospital of Montpellier, Gui de Chauliac Hospital, Montpellier, France.
Hermanowicz N; Department of Neurology, University of California Irvine, Irvine, California, USA.
Jech R; Department of Neurology, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic.
Jinnah HA; Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Kmiec T; Child Neurology Department, Children's Memorial Health Institute, Warsaw, Poland.
Lang A; Edmond J. Safra Program in Parkinson's Disease and the Department of Medicine (Neurology), Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada.
Martí MJ; Movement Disorders Unit, Hospital Clinic of Barcelona, European Reference Network for Rare Neurological Diseases (ERN-RND), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED. CB06/05/0018-ISCIII), Barcelona, Spain.
Mercimek-Andrews S; Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Monduy M; Neurology, Nicklaus Children's Hospital, Miami, Florida, USA.
Nimmo GAM; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Perez-Dueñas B; Department of Child Neurology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Pfeiffer HCV; Department of Child Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
Planellas L; Department of Neurology, Hospital Clinic of Barcelona, Barcelona, Spain.
Roze E; Department of Neurology, Sorbonne University, AP-HP Salpêtrière Hospital, Brain and Spine Institute, Paris, France.
Thakur N; Department of Pediatrics, Division of Child and Adolescent Neurology, University of Texas at Houston Medical School, Houston, Texas, USA.
Tochen L; Department of Neurology, Children's National Medical Center, Washington, District of Columbia, USA.
Vanegas-Arroyave N; Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Zorzi G; Department of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Burns C; Biostatistics, Retrophin, Inc., San Diego, California, USA.
Greblikas F; Research and Development, Retrophin, Inc., San Diego, California, USA.
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Źródło:
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Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2021 Jun; Vol. 36 (6), pp. 1342-1352. Date of Electronic Publication: 2020 Nov 16.
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Typ publikacji:
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Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2001->: New York, NY : Wiley-Liss
Original Publication: [New York, N.Y.] : Raven Press, [c1986-
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MeSH Terms:
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Pantothenate Kinase-Associated Neurodegeneration*/drug therapy
Pantothenate Kinase-Associated Neurodegeneration*/genetics
Activities of Daily Living ; Double-Blind Method ; Humans ; Pantothenic Acid/analogs & derivatives
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References:
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Contributed Indexing:
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Keywords: fosmetpantotenate; pantothenate kinase-associated neurodegeneration; randomized controlled trial; treatment
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Substance Nomenclature:
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19F5HK2737 (Pantothenic Acid)
VA101M0K2F (fosmetpantotenate)
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Entry Date(s):
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Date Created: 20201117 Date Completed: 20210623 Latest Revision: 20240402
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Update Code:
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20240402
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PubMed Central ID:
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PMC8246547
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DOI:
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10.1002/mds.28392
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PMID:
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33200489
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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.
(© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
