| Title | Safety and tolerability of a humanized rabbit monoclonal antibody (SSS07) in healthy adults: Randomized double -blind placebo-controlled single ascending dose trial |
| Authors | Liu, Chang Dong, Wenliang Xia, Lin Lv, Jie Jiang, Daoli Wang, Qian Wang, Mei Wu, Maofeng Miao, Jingwei Tao, Tao Wang, Dong Zheng, Lili Su, Shiguang Liu, Lizhong Fang, Yi |
| Affiliation | Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Phase Clin Res Unit 1, B24 Yinquan Rd, Qingyuan City 511518, Guangdong, Peoples R China Peking Univ, Dept Pharm, Peoples Hosp, Beijing 100034, Peoples R China Peking Univ, Sch Pharmaceut Sci, Dept Pharm Adm & Clin Pharm, Beijing 100191, Peoples R China Xuzhou Med Univ, Dept Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China Peking Univ, Dept Intens Care Units, Peoples Hosp, Beijing 100034, Peoples R China Xuzhou Med Univ, Affiliated Hosp, Dept Pharm, Xuzhou 221006, Jiangsu, Peoples R China Shenyang Sunshine Pharmaceut Co Ltd, Econ & Technol Dev Zone, Shenyang 110027, Liaoning, Peoples R China |
| Issue Date | Feb-2021 |
| Publisher | INTERNATIONAL IMMUNOPHARMACOLOGY |
| Abstract | Background/objective: SSS07, a humanized rabbit monoclonal antibody, can selectively block human tumor necrosis factor-alpha (TNF-alpha). The objective of this study was to assess the safety, tolerability, and relative immunogenicity of SSS07 after multiple single subcutaneous (SC) doses in healthy volunteers. Methods: A total of 71 healthy volunteers were randomized to six sequential ascending-dose groups (5, 15, 30, 50, 75, and 100 mg), and except for the 100 mg group that only had one subject who received a placebo, all of the other groups included two placebo-control subjects. Safety, tolerability, and immunogenicity were assessed by physical examinations, vital signs, electrocardiography (ECG), clinical laboratory tests, and plasma anti-drug antibody (ADA) over 28 days for each group. Their concentrations of TNF-alpha were also analyzed. Only after safety and tolerance were determined in the lower-dose groups was the next dose group initiated. The dose increments did not exceed 100 mg. Results: No serious adverse events or dose-limited toxicity (DLT) were observed, so 100 mg was defined as the maximum tolerated dose (MTD). Overall, 71 AEs and 59 treatment-related adverse events (TRAEs) were reported in 36 (60.0%) and 30 (50.0%) volunteers, respectively, who received SSS07. All AEs and TRAEs were mild or moderate and expected based on previous results with similar types of drugs, without new safety concerns. Except for infections and administration site reactions, the frequency and intensity of the other TRAEs were similar for SSS07 and placebo. No severe acute immune reactions occurred. The lower dose's immunogenicity was stronger than the higher doses. The highest ADA titer was observed 3 to 6 months after administration. Conclusion: SSS07 was generally safe and well tolerated in healthy Chinese volunteers. Higher immunogenicity was observed at low SSS07 concentration levels. The infections and administration site conditions might have been related to the immunogenicity and the degree of inhibition of TNF-alpha. However, the existence of ADA did not appear to affect the safety of the subjects throughout the follow-up period. These findings could support further investigations of treatments with humanized monoclonal antibodies. |
| URI | http://hdl.handle.net/20.500.11897/604621 |
| ISSN | 1567-5769 |
| DOI | 10.1016/j.intimp.2020.107263 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 药学院 |
