Abstract：
UNASSIGNED: SHR-1703 is a novel humanized IgG1 monoclonal antibody with high IL-5 affinity and prolonged half-life, aiming to control eosinophil-related diseases. The study intended to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of SHR-1703 in healthy subjects.
UNASSIGNED: A single-center, randomized, double-blind, placebo-controlled, single-dose escalation phase I study was conducted. 42 subjects were allocated to sequentially receive single subcutaneous injection of 20, 75, 150, 300, and 400 mg SHR-1703 or placebo.
UNASSIGNED: After administration, SHR-1703 was slowly absorbed with median Tmax ranging from 8.5 to 24.5 days. Mean t1/2 in 150 to 400 mg doses was 86 to 100 days. Cmax and AUC increased in nearly dose-proportional pattern over range of 75 to 400 mg SHR-1703. After receiving SHR-1703, peripheral blood eosinophils (EOS) greatly decreased from baseline, which showed no significant change from baseline in placebo group. Magnitude and duration of reduction of EOS rose with increased dosing of SHR-1703. In 400 mg dose, remarkable efficacy of reducing EOS maintained up to approximately 6 months post single administration. Moreover, SHR-1703 exhibited low immunogenicity (2.9%), favorable safety, and tolerability in healthy subjects.
UNASSIGNED: Pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of SHR-1703 support further clinical development of SHR-1703 in eosinophil-associated diseases.
UNASSIGNED: The study was registered on the ClinicalTrials.gov (identifier: NCT04480762).
UNASSIGNED: A single-center, randomized, double-blind, placebo-controlled, single-dose escalation phase I study was conducted. 42 subjects were allocated to sequentially receive single subcutaneous injection of 20, 75, 150, 300, and 400 mg SHR-1703 or placebo.
UNASSIGNED: After administration, SHR-1703 was slowly absorbed with median Tmax ranging from 8.5 to 24.5 days. Mean t1/2 in 150 to 400 mg doses was 86 to 100 days. Cmax and AUC increased in nearly dose-proportional pattern over range of 75 to 400 mg SHR-1703. After receiving SHR-1703, peripheral blood eosinophils (EOS) greatly decreased from baseline, which showed no significant change from baseline in placebo group. Magnitude and duration of reduction of EOS rose with increased dosing of SHR-1703. In 400 mg dose, remarkable efficacy of reducing EOS maintained up to approximately 6 months post single administration. Moreover, SHR-1703 exhibited low immunogenicity (2.9%), favorable safety, and tolerability in healthy subjects.
UNASSIGNED: Pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of SHR-1703 support further clinical development of SHR-1703 in eosinophil-associated diseases.
UNASSIGNED: The study was registered on the ClinicalTrials.gov (identifier: NCT04480762).
摘要：
■SHR-1703是一种新型的人源化IgG1单克隆抗体，具有高IL-5亲和力和延长的半衰期，旨在控制嗜酸性粒细胞相关疾病。这项研究旨在评估药代动力学，药效学,免疫原性,SHR-1703在健康受试者中的安全性和耐受性。
■单中心，随机化，双盲,安慰剂对照,进行单剂量递增I期研究.42名受试者被分配依次接受20、75、150、300和400mgSHR-1703或安慰剂的单次皮下注射。
■给药后，SHR-1703缓慢吸收，中位Tmax为8.5至24.5天。150至400mg剂量的平均t1/2为86至100天。在75至400mgSHR-1703的范围内,Cmax和AUC以接近剂量比例的模式增加。接收SHR-1703后,外周血嗜酸性粒细胞(EOS)较基线显著下降,与基线相比，安慰剂组无显著变化。EOS降低的幅度和持续时间随着SHR-1703剂量的增加而增加。在400毫克剂量中，在单次给药后约6个月内，降低EOS的显着疗效保持不变。此外，SHR-1703表现出低免疫原性（2.9％），在健康受试者中具有良好的安全性和耐受性。
■药代动力学，药效学,免疫原性,SHR-1703的安全性和耐受性支持SHR-1703在嗜酸性粒细胞相关疾病中的进一步临床发展。
■该研究已在ClinicalTrials.gov上注册（标识符：NCT04480762）。
■单中心，随机化，双盲,安慰剂对照,进行单剂量递增I期研究.42名受试者被分配依次接受20、75、150、300和400mgSHR-1703或安慰剂的单次皮下注射。
■给药后，SHR-1703缓慢吸收，中位Tmax为8.5至24.5天。150至400mg剂量的平均t1/2为86至100天。在75至400mgSHR-1703的范围内,Cmax和AUC以接近剂量比例的模式增加。接收SHR-1703后,外周血嗜酸性粒细胞(EOS)较基线显著下降,与基线相比，安慰剂组无显著变化。EOS降低的幅度和持续时间随着SHR-1703剂量的增加而增加。在400毫克剂量中，在单次给药后约6个月内，降低EOS的显着疗效保持不变。此外，SHR-1703表现出低免疫原性（2.9％），在健康受试者中具有良好的安全性和耐受性。
■药代动力学，药效学,免疫原性,SHR-1703的安全性和耐受性支持SHR-1703在嗜酸性粒细胞相关疾病中的进一步临床发展。
■该研究已在ClinicalTrials.gov上注册（标识符：NCT04480762）。
