Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial
Huijie Bian, Liang Chen, Zhaohui Zheng, Xiuxuan Sun, Jiejie Geng, Ruo Chen, Ke Wang, Xu Yang, Shirui Chen, Siyu Chen, Xie Rong-hua, Kui Zhang, Jinlin Miao, Junfeng Jia, Hao Tang, Shuangshuang Liu, Hongwei Shi, Yong Yang, Xiaochun Chen, Vinay Malhotra, Nosheen Nasir, Iffat Khanum, Faisal Mahmood, Saeed Hamid, Claudio Stadnik, Kengi Itinose, Caroline Cândida Carvalho de Oliveira, Cesar Dusilek, Lucas Rivabem, Adilson Joaquim Westheimer Cavalcante, Suzara Souto Lopes, Wladmir Faustino Saporito, Fábio José Concilio Fucci, Jesus Abraham Simón Campos, Ling Wang, Linna Liu, Qingyi Wang, Ding Wei, Zheng Zhang, Zhi‐Nan Chen, Ping Zhu
Abstract
Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.