A Randomized, Double-Blind, 2-Treatment, 2-Period, Crossover Phase 1 Study to Compare the Pharmacokinetics, Safety and Tolerability of 60 IU/Kg of Abcertin and Cerezyme in Healthy Volunteers Following a Single Intravenous Administration

一项随机、双盲、两治疗、两周期、交叉设计的I期研究,旨在比较健康志愿者单次静脉注射60 IU/Kg Abcertin和Cerezyme后的药代动力学、安全性和耐受性。

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Abstract

BACKGROUND: Imiglucerase (Cerezyme; Sanofi, Paris, France), an analogue of β-glucocerebrosidase produced by recombinant DNA technology, has been a safe and effective treatment for Gaucher disease (GD) for over 25 years. A new imiglucerase, Abcertin (Seongnam-si, Gyeonggi-do, Republic of Korea) has shown a similar safety and efficacy profile in previous clinical studies. This study compared the pharmacokinetics, immunogenicity, safety, and tolerability to EU-sourced Cerezyme following a single 60 IU/kg dose. METHODS: This phase 1, single-center, randomized, double-blind, two-way crossover study enrolled 36 healthy volunteers aged 18-45 years. Participants were randomly assigned to receive either Abcertin or Cerezyme in a predetermined sequence. RESULTS: Abcertin reached peak plasma concentrations at a median t(max) of 61 min (range: 40-121 min). The mean C(max), AUC(0-last), and AUC(0-inf) were 115.4 mU/mL, 12,190 min·mU/mL, and 12,210 min mU/mL, respectively, indicating bioequivalence to Cerezyme. The mean t(½), CL, and V(z) were 6.88 min, 376.7 mL/min, and 3.62 L, respectively, and were comparable between the two treatments. One participant in the Cerezyme group developed anti-drug antibodies, which were non-neutralizing A total of 24 subjects experienced treatment-emergent adverse event (TEAE). The most common TEAE was headache (3 in the Abcertin group and 5 in the Cerezyme group), followed by general disorders and administration site condition (3 in Abcertin group and 5 in Cerezyme group). Two participants in the Cerezyme sequence experienced severe TEAEs: one had a urinary tract infection, and the other developed urticaria, which leading to study withdrawal. CONCLUSION: Abcertin demonstrated pharmacokinetic equivalence to Cerezyme, with a comparable safety, immunogenicity, and tolerability profile. These findings support its potential as an affordable biosimilar for GD treatment.

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