Orphanet journal of rare diseases · 2025
A phase 4, open-label, multicenter study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease.
СтатьяМногоцентровое исследованиеКлиническое исследование IV фазыНазвание и аннотация: Перевод в очереди
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Ren Hong, Zhang Wei, Ouyang Yan, Guo Junhong, Xu Hong, Ma Jie, Luo Xiaoping, Pan Xiaoxia, Yuan Yun, Zhang Wei, Shen Qian, Li Bin, Feng Qiqi, Liu Shi, Chen Nan
Аннотация
BACKGROUND: This is the first phase 4 study evaluating safety and efficacy of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease, and exploring the impact of COVID-19 infection on the prognosis of Fabry disease under ERT.
METHODS AND RESULTS: Eligible patients received an infusion of agalsidase beta (1.0 mg/kg/2w) for up to 48 weeks. The primary endpoint was the safety of agalsidase beta. The endpoints of efficacy included changes in plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), symptoms and estimated glomerular filtration rate (eGFR) from baseline to week 48. A post-hoc subgroup analysis was conducted by age group (< 30 years and ≥ 30 years) and in patients with or without COVID-19 infection. All 22 patients completed the study and 14 of them were infected by COVID-19. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%). Mean plasma GL-3 (-34.6%) and Lyso-GL-3 (-60.3%) levels decreased from baseline to week 48. Thirteen participants (59.1%) experienced improved specific symptoms at week 48. There were no meaningful changes in eGFR during the study, and the overall population showed an annual eGFR slope of 0.43 mL/min/1.73 m2/year (95% CI: -5.95 to 6.82). In the subgroup analysis, the reductions in plasma GL-3 and Lyso-GL-3 levels, improvement in symptoms, and attenuation of eGFR decline after 48 weeks of treatment were generally greater in patients aged < 30 years (n = 11) than in patients aged ≥ 30 years (n = 11), and less pronounced in the COVID-19 infected group (n = 14) than in the uninfected group (n = 8).
CONCLUSIONS: This study demonstrates that agalsidase beta is safe and effective in Chinese patients with Fabry disease, and suggestes that COVID-19 infection may potentially impact the renal prognosis for Fabry disease.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT05054387. Registered 09 September 2021, https://clinicaltrials.gov/study/NCT05054387.
METHODS AND RESULTS: Eligible patients received an infusion of agalsidase beta (1.0 mg/kg/2w) for up to 48 weeks. The primary endpoint was the safety of agalsidase beta. The endpoints of efficacy included changes in plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), symptoms and estimated glomerular filtration rate (eGFR) from baseline to week 48. A post-hoc subgroup analysis was conducted by age group (< 30 years and ≥ 30 years) and in patients with or without COVID-19 infection. All 22 patients completed the study and 14 of them were infected by COVID-19. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%). Mean plasma GL-3 (-34.6%) and Lyso-GL-3 (-60.3%) levels decreased from baseline to week 48. Thirteen participants (59.1%) experienced improved specific symptoms at week 48. There were no meaningful changes in eGFR during the study, and the overall population showed an annual eGFR slope of 0.43 mL/min/1.73 m2/year (95% CI: -5.95 to 6.82). In the subgroup analysis, the reductions in plasma GL-3 and Lyso-GL-3 levels, improvement in symptoms, and attenuation of eGFR decline after 48 weeks of treatment were generally greater in patients aged < 30 years (n = 11) than in patients aged ≥ 30 years (n = 11), and less pronounced in the COVID-19 infected group (n = 14) than in the uninfected group (n = 8).
CONCLUSIONS: This study demonstrates that agalsidase beta is safe and effective in Chinese patients with Fabry disease, and suggestes that COVID-19 infection may potentially impact the renal prognosis for Fabry disease.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT05054387. Registered 09 September 2021, https://clinicaltrials.gov/study/NCT05054387.