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

BACKGROUND This 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). METHODS We 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. FINDINGS A total of 1,222 participants were randomized and dosed (SA58, n=901; placebo, n=321). Median of follow-up was 2·25 days and 2·79 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=0·49). All adverse events were mild in severity. Laboratory-confirmed symptomatic COVID-19 developed in 7 of 824 participants (0·22 per 100 person-days) in the SA58 group vs 14 of 299 (1·17 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 80 · 82% (95%CI 52 · 41%-92 · 27%). There were 32 SARS-CoV-2 RT-PCR positives (1·04 per 100 person-days) in the SA58 group vs 32 (2·80 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 61·83% (95%CI 37· 50%-76· 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·7. INTERPRETATION SA58 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. FUNDING No funding was received for this study. Evidence before this study Monoclonal 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 study During a recent large outbreak of the Omicron BF·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 80·82% (95%CI 52·41%-92·27%) and of SARS-CoV-2 infection by 61·83% (95%CI 37·50%-76·69%) in our study participants. Implications of all the available evidence This 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. ### Competing Interest Statement Xiaoliang Xie and Yunlong Cao are the inventors of the provisional patent applications for the anti-COVID-19 monoclonal antibody (SA58). Xiaoliang Xie and Yunlong Cao are founders of Singlomics Biopharmaceuticals. SA58 have been transferred to Sinovac Biotech for clinical development. Gang Zeng, Jianxing Yu, Xing Meng, and Weidong Yin are employees of Sinovac Biotech. Jing Li and Xiaojuan Lian are employees of Sinovac Life Sciences. All other authors declare no competing interests. ### Clinical Trial NCT05667714 ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The clinical trial protocol and informed consent form were approved by the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (reference no., DTEC-YW2022-024-01). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.