In our previous nonclinical study of SCTA01, no ADE response or ADCC phenomenon was detected (20)
In our previous nonclinical study of SCTA01, no ADE response or ADCC phenomenon was detected (20). the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases inCmaxand AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifierNCT04483375.) KEYWORDS:COVID-19, SARS-CoV-2, monoclonal antibody, safety, pharmacokinetics == INTRODUCTION == Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and manifesting as respiratory Lysionotin tract infection with severe multiorgan dysfunction, has become a worldwide pandemic since the first reported case in December 2019 (1). The number of confirmed cases of COVID-19 has exceeded 103 million, with over 2 million deaths as of 1 February 2020 (2). Remdesivir, a nucleotide prodrug of an adenosine analog, is currently the only drug approved for the treatment of COVID-19 (3), and efficacious therapeutic strategies for COVID-19 are still largely lacking. Antibody-based passive immunotherapies, including convalescent-phase plasma and monoclonal antibodies, are reported to be promising treatment options for COVID-19 as they neutralize SARS-CoV-2 by primarily targeting the receptor-binding domain (RBD) of the spike protein, which mediates its entry into the host cells (413). Previous studies have shown that convalescent-phase plasma is associated with improved viral load suppression, clinical symptoms, and survival in the treatment of COVID-19 (613). However, the collection of sufficient plasma from infected COVID-19 patients is not always feasible and practical. Thus, monoclonal antibodies are highly expected to play a critical role in fighting against COVID-19. Currently, more than 20 anti-SARS-CoV-2 monoclonal antibodies are being investigated in the preclinical and clinical trials (14). Based on the clinical benefits and verified viral load decline in outpatient trials, an antibody cocktail consisting of casirivimab plus imdevimab and bamlanivimab as a monotherapy were approved by the U.S. Food and Drug Administration in November 2020 for emergency use to treat patients with mild to moderate COVID-19 symptoms (5,15,16). Although bamlanivimab alone failed to demonstrate a clinical benefit for hospitalized COVID-19 patients without end-stage organ failure (17), a combination of bamlanivimab with etesevimab significantly reduced Pbx1 hospitalizations and deaths among high-risk patients recently diagnosed with COVID-19 (18). Increasing evidence suggests that anti-SARS-CoV-2 monoclonal antibodies are efficacious in the prevention and treatment of COVID-19 (19). SCTA01, also named HB27, is a newly developed monoclonal antibody of the IgG1 subtype with functions similar to those of bamlanivimab but possesses unique features (20). The Fc-mutated (LALA) Lysionotin modification of SCTA01 not only reduces antibody-dependent enhancement (ADE) and antibody-dependent cell cytotoxicity (ADCC) but also guarantees its high-affinity neutralizing responses (see Fig. S1 in the supplemental material) (20). Our previousin vitrostudy validated the neutralizing activity of SCTA01 with a classical plaque reduction neutralization test value of 0.22 nM (20). In addition, both prophylactic and therapeutic efficacies of SCTA01 were demonstrated in animal experiments (20). Specifically, a single dose of 20 mg/kg administered either before or 2 h after SARS-CoV-2 exposure resulted in >99.9% reduction of the viral RNA load 5 days postinfection in the lungs and trachea in the mouse model, accompanied by alleviation of pulmonary pathological damage (20). In the rhesus monkey model, no obvious adverse events (AE) were observed when SCTA01 was administered at 10 times the effective dose (500 mg/kg) (20). Based on these encouraging findingsin vitroand in animal models, this randomized, double-blind, placebo-controlled phase I study was carried out to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of SCTA01 targeting SARS-CoV-2 in healthy adults. == Lysionotin RESULTS == == Demographics and baseline characteristics of the participants. == Overall, 33 participants (22 males and 11 females with an average age.