Abstract：
RTH258 (brolucizumab) is a humanized single chain antibody fragment, the smallest functional unit of an antibody designed to target vascular endothelial growth factor in angiogenic retinal disease. To further understand the safe use of RTH258, this study assessed the potential impact of intravitreal RTH258 on pre- and postnatal development in the offspring of cynomolgus monkeys following administration to the mother. Three groups of 16 pregnant females were included: a low dose group (RTH258 3 mg/50 µl [60 mg/ml]), a high dose group (RTH258 6 mg/50 µl [120 mg/ml]), and a control group. Maternal animals were administered a single injection of 50 µl in the right eye once every four weeks. Animals were observed daily and detailed observations were collected before and after the first dose, and then weekly thereafter. Following parturition, observations of infants included external, morphological, and ophthalmic examinations; neurobehavioral test battery; grip strength; and skeletal development. Blood samples for hematology, coagulation, and clinical chemistry were collected from non-fasted maternal and infant animals. No RTH258-related deaths occurred in maternal dams or infants. No RTH258-related clinical observations were noted in maternal animals or in surviving infants - there were no changes in gestation length; pregnancy loss; deaths; body weight/weight change; infant grip strength; infant external, morphological, or skeletal evaluations; ophthalmoscopy or neurobehavioral observations; or clinical pathology parameters. RTH258 had no impact on pregnancy or parturition; embryo-fetal development; or survival, growth, or postnatal development of offspring when administered via repeated intravitreal administration.
摘要：
RTH258（brolucizumab）是一种人源化单链抗体片段，在血管生成性视网膜疾病中，设计用于靶向血管内皮生长因子的抗体的最小功能单位。为了进一步了解RTH258的安全使用，本研究评估了玻璃体内RTH258对母亲给药后食蟹猴后代出生前和出生后发育的潜在影响。包括三组16名孕妇：低剂量组（RTH2583mg/50μl[60mg/ml]），高剂量组（RTH2586mg/50μl[120mg/ml]），和一个对照组。每四周一次在母畜右眼中单次注射50μl。每天观察动物，并在第一次给药之前和之后收集详细的观察结果，此后每周一次。分娩后,对婴儿的观察包括外部，形态学,和眼科检查；神经行为测试电池；握力；和骨骼发育。血液学的血样,凝血,和临床化学是从非禁食的母婴动物中收集的。在产妇或婴儿中没有发生与RTH258相关的死亡。在母体动物或存活的婴儿中没有发现与RTH258相关的临床观察-妊娠长度没有变化;妊娠损失;死亡;体重/体重变化;婴儿握力;婴儿外部,形态学,或骨骼评估；检眼镜或神经行为观察；或临床病理参数。RTH258对妊娠或分娩没有影响;胚胎-胎儿发育;或存活，增长,或通过反复玻璃体内给药时后代的出生后发育。
