Fc-Modified Antibody in Hospitalized Severe COVID-19 Patients

<b>Background:</b> Hospitalized patients with severe COVID-19 are at high risk of clinical deterioration. <b>Methods:</b> A global, randomized, double-blinded, and placebo-controlled phase II trial that investigated the clinical efficacy of SCTA01, an Fc-modified monoclonal antibody, in patients hospitalized with severe COVID-19 during the Delta variant wave was performed. The primary outcome was time to clinical improvement up to Day 29. Secondary outcomes measured the all-cause mortality rate up to Day 29, time to SARS-CoV-2 RNA negativity up to Day 29, and the number of antibody-dependent enhancements. <b>Results:</b> From 27 March 2021, to 11 February 2022, 102 hospitalized adults with severe COVID-19 received a single intravenous infusion of SCTA01 15 mg/kg or 50 mg/kg or placebo in a 1:1:1 ratio. The median time to clinical improvement in the SCTA01 group was numerically shorter than that in the placebo group; however, the between group difference was statistically non-significant (SCTA01 15 mg/kg vs. placebo, HR 0.99, 95% CI 0.55-1.77, <i>p</i> = 0.742; SCTA01 50 mg/kg vs. placebo, HR 1.07, 95% CI 0.61-1.88, <i>p</i> = 0.095). The median time to achieve a negative SARS-CoV-2 status was shorter in the SCTA01 15 mg/kg group (14.0 days vs. 27.0 days) but not in the SCTA01 50 mg/kg group (28.0 days vs. 27.0 days) compared to the placebo group. Adverse events were comparable across all groups, and no treatment-related serious adverse event or antibody-dependent enhancement was reported. <b>Conclusions:</b> The Fc-modified antibody was safe but lacked significant clinical efficacy in vivo, likely due to the SARS-CoV-2 viral mutation.