RT Journal Article
SR Electronic
T1 A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e2109
OP e2117
DO 10.1212/WNL.0000000000006932
VO 92
IS 18
A1 Hanns Lochmüller
A1 Anthony Behin
A1 Yoseph Caraco
A1 Heather Lau
A1 Massimiliano Mirabella
A1 Ivailo Tournev
A1 Mark Tarnopolsky
A1 Oksana Pogoryelova
A1 Catherine Woods
A1 Alexander Lai
A1 Jinay Shah
A1 Tony Koutsoukos
A1 Alison Skrinar
A1 Hank Mansbach
A1 Emil Kakkis
A1 Tahseen Mozaffar
YR 2019
UL http://n.neurology.org/content/92/18/e2109.abstract
AB Objective To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy.Methods UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy–Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results.Results Eighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER −2.25 kg vs placebo −2.99 kg; LSM difference confidence interval [CI] 0.74 [−1.61 to 3.09]; p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) −1.49 (−5.83 to 2.86); knee extension strength −0.40 (−2.38 to 1.58); and GNEM-FAS mobility domain score −0.72 (−2.01 to 0.57). Gastrointestinal events were the most common AEs.Conclusions Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy.Classification of evidence This study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.6MWT=6-minute walk test; Ace-ER=aceneuramic acid extended-release; AE=adverse event; CI=confidence interval; GNEM-DMP=GNE myopathy disease monitoring program; GNEM-FAS=GNE myopathy–Functional Activity Scale; HHD=hand-held dynamometer; LE=lower extremity; LEC=lower extremity composite; LSM=least squares mean; ManNAc=N-acetyl-d-mannosamine; SA=sialic acid; SAE=serious adverse event; UE=upper extremity; UEC=upper extremity composite