AUTHOR=Niu Suping , Chen Min , Yan Diqin , Liu Xiangxing , Guo Shuren , Ou Lun , Fan Huaying , Lv Jie , Wang Qian , Dong Wenliang , Xia Lin , Wang Simin , Liu Gang , Gu Qun , Guo Danjie , Liu Hongxia , Rao Huiying , Zheng Qingshan , Nie Xiaoyan , Song Haifeng , Fang Yi 

TITLE=A Randomized Controlled Dose-Escalation Study of LY06006, a Recombinant Humanized Monoclonal Antibody to RANKL, in Chinese Healthy Adults

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.893166

DOI=10.3389/fphar.2022.893166

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> This study was conducted to explore the safety, tolerance, pharmacokinetics, pharmacodynamics, and immunogenicity of LY06006, a recombinant humanized monoclonal antibody to RANKL, when administrated subcutaneously in Chinese healthy adults.</p><p><bold>Research design and methods:</bold> This was a randomized, double-blinded, placebo-controlled, single ascending dose study performed in 32 healthy Chinese adults, who were randomly assigned to receive a single injection dose of 18, 60, 120 mg study drug or placebo with a follow-up of 140–252 days.</p><p><bold>Results:</bold> No deaths or drug-related serious adverse events occurred. LY06006 was rapidly absorbed in the 60 mg group with a T<sub>max</sub> range of 120–480 h and serum LY06006 concentrations decreased slowly 11–13 days after dosing with a long mean (SD) half-life of 389.58 (63.44) h. The most frequent AEs were elevated serum parathyroid hormone (PTH) level (83.3%), hypocalcemia (54.2%), and hypophosphatemia (45.8%). None of the 32 subjects tested positive for anti-drug antibody during the trial.</p><p><bold>Conclusion:</bold> Single-dose subcutaneous administration of LY06006 was safe and well-tolerated in healthy Chinese adults. C<sub>max</sub> showed linear pharmacokinetic characteristics in the dose range of 18–120 mg based on dose-exposure proportionality analysis.</p>