Dataset Information

Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.

ABSTRACT: GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.Evaluate the safety and efficacy of SA (delivered by aceneuramic acid extended-release [Ace-ER]) as treatment for GNEM.A Phase 2, randomized, double-blind, placebo-controlled study evaluating Ace-ER 3?g/day or 6?g/day versus placebo was conducted in GNEM subjects (n?=?47). After the first 24 weeks, placebo subjects crossed over to 3?g/day or 6?g/day for 24 additional weeks (dose pre-assigned during initial randomization). Assessments included serum SA, muscle strength by dynamometry, functional assessments, clinician- and patient-reported outcomes, and safety.Dose-dependent increases in serum SA levels were observed. Supplementation with Ace-ER resulted in maintenance of muscle strength in an upper extremity composite (UEC) score at 6?g/day compared with placebo at Week 24 (LS mean difference +2.33?kg, p?=?0.040), and larger in a pre-specified subgroup able to walk ?200?m at Screening (+3.10?kg, p?=?0.040). After cross-over, a combined 6?g/day group showed significantly better UEC strength than a combined 3?g/day group (+3.46?kg, p?=?0.0031). A similar dose-dependent response was demonstrated within the lower extremity composite score, but was not significant (+1.06?kg, p?=?0.61). The GNEM-Functional Activity Scale demonstrated a trend improvement in UE function and mobility in a combined 6?g/day group compared with a combined 3?g/day group. Patients receiving Ace-ER tablets had predominantly mild-to-moderate AEs and no serious adverse events.This is the first clinical study to provide evidence that supplementation with SA delivered by Ace-ER may stabilize muscle strength in individuals with GNEM and initiating treatment earlier in the disease course may lead to better outcomes.

SUBMITTER: Argov Z

PROVIDER: S-EPMC5271423 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.

Argov Zohar Z Caraco Yoseph Y Lau Heather H Pestronk Alan A Shieh Perry B PB Skrinar Alison A Koutsoukos Tony T Ahmed Ruhi R Martinisi Julia J Kakkis Emil E

Journal of neuromuscular diseases 20160301 1

<h4>Background</h4>GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.<h4>Objective</h4>Evaluate the safety and efficacy of SA (delivered by aceneuramic acid extended-release [Ace-ER]) as treatment for GNEM.<h4>Methods</h4>A Phase 2, randomized, double-blind, placebo-controlled study evaluating Ace-ER 3 g/day or 6 g/day versus placebo was conducted in GNEM subjects (n = 47). After the first 24 weeks, placebo subjects crossed ove ...[more]

PMID: 27854209

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Project description:BackgroundStroke patients are often affected by arm paresis, have functional impairments and receive help from professional or informal caregivers. Progressive resistance training is a common intervention for functional impairments after paresis. Randomised controlled trials (RCT) showed benefits for functional recovery after resistance training. However, there is a lack of evidence for strength training in subacute stroke patients. The aim of this study is to investigate safety and effectiveness of arm strength training in subacute stroke patients.MethodsWe will conduct a prospective, assessor-blinded RCT of people with subacute stroke. We will randomly assign patients to one of two parallel groups in a 1:1 ratio and will use concealed allocation. The intervention group will receive, in addition to standard treatment, high-intensity arm training (three times per week, over three weeks; 60 min each session; with a total of nine additional sessions). The control group will receive, in addition to standard treatment, low-intensity arm training (same quantity, frequency and treatment time as the intervention group). Standard treatment for the affected arm includes mobilisation, stretching, therapeutic positioning, arm and hand motor training, strengthening exercises, mechanical assisted training, functional training and task-oriented training. The primary efficacy endpoint will be grip strength. Secondary outcome measures will be Modified Ashworth Scale, Motricity Index, Fugl-Meyer Assessment for the upper limb, Box and Block Test and Goal Attainment Scale for individual participatory goals. We will measure primary and secondary outcomes with blinded assessors at baseline and immediately after three weeks of additional therapy. Based on our sample size calculation, 78 patients will be recruited from our rehabilitation hospital in two and a half years. Drop-out rates and adverse events will be systematically recorded.DiscussionThis study attempts to close the evidence gap for effects of arm strength training in subacute stroke patients. The results of this trial will provide robust evidence for effects and safety of high-intensity arm training for people with stroke.Trial registrationGerman Clinical Trials Register, DRKS00012484 . Registered on 26 May 2017.

Project description:GNE myopathy is a slowly progressive autosomal recessive myopathy caused by mutations in the GNE (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) gene. This study aimed to (1) develop a nationwide patient registry for GNE myopathy in order to facilitate the planning of clinical trials and recruitment of candidates, and (2) gain further insight into the disease for the purpose of improving therapy and care.Medical records of genetically-confirmed patients with GNE myopathy at the National Center Hospital of the National Center of Neurology and Psychiatry (NCNP) were retrospectively reviewed in order to obtain data reflecting the severity and progression of the disease. We also referred to items in the datasheet of the nationwide registry of dystrophinopathy patients in the Registry of Muscular Dystrophies (Remudy). Items selected for the registration sheet included age, sex, age at onset, past history and complications, family history, body weight and height, pathological findings of muscle biopsy, grip power, walking ability, respiratory function, cardiac function, willingness to join upcoming clinical trials, and participation in patient associations. A copy of the original genetic analysis report was required of each patient.We successfully established the Remudy-GNE myopathy. Currently, 121 patients are registered nationwide, and 93 physicians from 73 hospitals collaborated to establish the registry. The mean age at onset was 27.7?±?9.6 years, and 19.8% (24/121) of patients could walk without assistance. Mean presumed durations from onset to use of assistive devices (cane and/or braces) and a wheelchair, and loss of ambulation were 12.4, 15.2, and 21.1 years, respectively. Three patients had a past history and/or complication of idiopathic thrombocytopenia. To share the progress of this study with the community, newsletters were published on a regular basis, and included information regarding new phase I clinical trials for GNE myopathy. The newsletters also served as a medium to bring attention to the importance of respiratory evaluation and care for respiratory insufficiency.The Japanese Remudy-GNE myopathy is useful for clarifying the natural history of the disease and recruiting patients with genetically-confirmed GNE myopathy for clinical trials.

Dataset Information

Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.

Publications

Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.

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