Post-Exposure Prophylaxis with SA58 (anti-COVID-19 monoclonal antibody) Nasal Spray for the prevention of symptomatic Coronavirus Disease 2019 in healthy adult workers: A randomized, single-blind, placebo-controlled clinical study

BACKGROUNDThis study has assessed a new Anti-COVID-19 Monoclonal Antibody Nasal Spray (SA58) for post-exposure prophylaxis (PEP) against symptomatic coronavirus disease 2019 (COVID-19). METHODSWe conducted an efficacy study in adults aged 18 years and older within three days of exposure to a SARS-CoV-2 infected individual. Recruited participants were randomized in a ratio of 3:1 to receive SA58 or placebo. Primary endpoints were laboratory-confirmed symptomatic COVID-19 within study period. FINDINGSA total of 1,222 participants were randomized and dosed (SA58, n=901; placebo, n=321). Median of follow-up was 2{middle dot}25 days and 2{middle dot}79 days for SA58 and placebo, respectively. Adverse events occurred in 221 of 901 (25%) and 72 of 321 (22%) participants with SA58 and placebo, respectively, with no significant difference (P=0{middle dot}49). All adverse events were mild in severity. Laboratory-confirmed symptomatic COVID-19 developed in 7 of 824 participants (0{middle dot}22 per 100 person-days) in the SA58 group vs 14 of 299 (1{middle dot}17 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 80 {middle dot} 82% (95%CI 52 {middle dot} 41%-92 {middle dot} 27%). There were 32 SARS-CoV-2 RT-PCR positives (1{middle dot}04 per 100 person-days) in the SA58 group vs 32 (2{middle dot}80 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 61{middle dot}83% (95%CI 37{middle dot} 50%-76{middle dot} 69%). A total of 21 RT-PCR positive samples were sequenced. 21 lineages of SARS-CoV-2 variants were identified, and all were the Omicron variant BF{middle dot}7. INTERPRETATIONSA58 Nasal Spray showed favorable efficacy and safety in preventing SARS-CoV-2 infection or symptomatic COVID-19 in healthy adult workers who had exposure to SARS-CoV-2 within 72 hours. FUNDINGNo funding was received for this study. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSMonoclonal antibodies (mAbs) and the post-exposure prophylaxis (PEP) with mAbs represent a very important public health strategy against COVID-19 outbreak. SA58 Nasal Spray is a broad-spectrum anti-COVID-19 mAb, developed by Sinovac Life Sciences Ltd. for treatment and prophylaxis against COVID-19. SA58 has been shown to potently neutralize ACE2-utilizing sarbecoviruses, including most of circulating Omicron variants. We searched PubMed on Nov 21, 2022, for published clinical trials, with no language or date restrictions, using various combinations of the search terms of "monoclonal antibodies", "SARS-CoV-2", "COVID-19", "prophylaxis", and "prevention". Three published trials were identified. The first study reported the efficacy of AZD7442 (tixagevimab/cilgavimab) PEP against symptomatic COVID-19 in adults aged [≥]18 years over a 183-day follow-up period. The primary efficacy end point of post-exposure prevention of symptomatic COVID-19 was not met, though AZD7442 showed promising results in participants who were SARS-CoV-2 RT-PCR negative at baseline. The second study reported the efficacy and safety of bamlanivimab for COVID-19 prevention in household contacts of individuals with a SARS-CoV-2 infection in a high-risk transmission setting over a one-month efficacy assessment period. The third study reported REGEN-COV (casirivimab/imdevimab) for preventing symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Both bamlanivimab and REGEN-COV showed satisfactory safety profile and efficacy against COVID-19 and were licensed for PEP use in the U.S. However, due to the circulating Omicron variants have developed significant escape properties, the emergency use authorization of bamlanivimab and REGEN-COV for treatment and PEP against COVID-19 has been discontinued by the U.S. Food and Drug Administration. Till the end of December 2022, no drug was available for PEP use against COVID-19. Added value of this studyDuring a recent large outbreak of the Omicron BF{middle dot}7 sublineage in Beijing, our preliminary results in healthy adults within 72 hours of contact with SARS-CoV-2-infected individuals showed that SA58 nasal spray was highly effective in preventing symptomatic COVID-19 and SARS-CoV-2 infection caused by the sublineage, which variants have shown significant escape of immunity in previous studies. SA58 was able to significantly lower the risk of laboratory-confirmed COVID-19 by 80{middle dot}82% (95%CI 52{middle dot}41%-92{middle dot}27%) and of SARS-CoV-2 infection by 61{middle dot}83% (95%CI 37{middle dot}50%-76{middle dot}69%) in our study participants. Implications of all the available evidenceThis trial showed the ability of a nasal spray of broad-spectrum anti-COVID-19 mAb SA58 to provide satisfactory protection against one circulating Omicron strain of SARS-CoV-2. The drug had a favorable safety profile and was well tolerated by healthy adults. This newly developed mAb is resistant to SARS-CoV-2 mutations and may provide a new powerful countermeasure to tackle against the immunity-escaping variants of SARS-CoV-2 circulating in the population. The intranasal administration of SA58 is novel and has many advantages over intramuscular injections of mAbs previously licensed, as it is less invasive and more acceptable in recipients. Auto-administration with easiness of use may allow early administration, probably a key feature for prevention.