Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan
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- Naoki Suzuki
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Madoka Mori-Yoshimura
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
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- Masahisa Katsuno
- Department of Neurology, Nagoya University Hospital, Nagoya, Japan
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- Masanori P. Takahashi
- Department of Neurology, Osaka University Hospital, Osaka, Japan
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- Satoshi Yamashita
- Department of Neurology, Kumamoto University Hospital, Kumamoto, Japan
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- Yasushi Oya
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
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- Atsushi Hashizume
- Department of Neurology, Nagoya University Hospital, Nagoya, Japan
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- Shinichiro Yamada
- Department of Neurology, Nagoya University Hospital, Nagoya, Japan
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- Masayuki Nakamori
- Department of Neurology, Osaka University Hospital, Osaka, Japan
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- Rumiko Izumi
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Masaaki Kato
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Hitoshi Warita
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Maki Tateyama
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Hiroshi Kuroda
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Ryuta Asada
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan
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- Takuhiro Yamaguchi
- Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan
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- Ichizo Nishino
- Department of Neuromuscular Research, National Institute of Neuroscience and Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
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- Masashi Aoki
- Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
抄録
<jats:p>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.</jats:p>
収録刊行物
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- Journal of Neuromuscular Diseases
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Journal of Neuromuscular Diseases 10 (4), 555-566, 2023-07-04
IOS Press
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詳細情報 詳細情報について
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- CRID
- 1360580230621962496
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- ISSN
- 22143602
- 22143599
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- データソース種別
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- Crossref
- KAKEN