Dataset Information

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

ABSTRACT:

Background

GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. No treatment has been established so far.

Objective

We evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy.

Methods

This multicenter, placebo-controlled, double-blind study comprised genetically confirmed GNE myopathy patients in Japan who were randomly assigned into treatment groups of sialic acid-extended release (SA-ER) tablets (6 g/day for 48 weeks) or placebo groups (4:1). The primary endpoint of effectiveness was set as the change in total upper limb muscle strength (upper extremity composite [UEC] score) from the start of administration to the final evaluation time point.

Results

Among the 20 enrolled patients (SA-ER group, 16; placebo group, 4), 19 completed this 48-week study. The mean value of change in UEC score (95% confidence interval [CI]) at 48 weeks was -0.1 kg (-2.1 to 2.0) in the SA-ER group and -5.1 kg (-10.4 to 0.3) in the placebo group. The least squares mean difference (95% CI) between the groups in the covariance analysis was 4.8 kg (-0.3 to 9.9; P = 0.0635). The change in UEC score at 48 weeks was significantly higher in the SA-ER group compared with the placebo group (P = 0.0013) in the generalized estimating equation test repeated measurement analysis. In one patient in the SA-ER group, who was found to be pregnant 2 weeks after drug administration fetal death with tangled umbilical cord occurred at 13 weeks after the discontinuation of treatment. No other serious adverse effects were observed.

Conclusions

The present study indicates that oral administration of SA-ER tablets is effective and safe in patients with GNE myopathy in Japan.

SUBMITTER: Suzuki N

PROVIDER: S-EPMC10357206 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

Suzuki Naoki N Mori-Yoshimura Madoka M Katsuno Masahisa M Takahashi Masanori P MP Yamashita Satoshi S Oya Yasushi Y Hashizume Atsushi A Yamada Shinichiro S Nakamori Masayuki M Izumi Rumiko R Kato Masaaki M Warita Hitoshi H Tateyama Maki M Kuroda Hiroshi H Asada Ryuta R Yamaguchi Takuhiro T Nishino Ichizo I Aoki Masashi M

Journal of neuromuscular diseases 20230101 4

<h4>Background</h4>GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. No treatment has been established so far.<h4>Objective</h4>We evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy.<h4>Methods</h4>This multicenter, placebo-controlled, double-blind study comprised genetically confirmed GNE myopathy patients in Japan who were randomly a ...[more]

PMID: 37125562

Similar Datasets

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

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

Background

Objective

Methods

Results

Conclusions

Publications

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

Similar Datasets

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