A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers

Abstract

ABSTRACTSuccessful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP™) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP™ exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP™ or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP™ was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP™ were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP™ application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP™ was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP™ can be considered an integral instrument for COVID-19 prevention.