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Abstract The SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. BioBlock is a nasal spray of anti-SARS-CoV-2 preparation based on virus-neutralising antibodies prepared from colostrum from cows immunised with SARS-CoV-2 spike protein. This triple-blind placebo-controlled cluster randomised parallel trial seeks to evaluate the efficacy of a BioBlock spray in the prevention and treatment of SARS-CoV-2 infection. Laboratory-confirmed COVID-19 cases and their household members will be randomly allocated to each of either the intervention (BioBlock nasal spray) or the placebo (nasal spray) arms. The intervention is a 14-day course of nasal spray used by index case and household contacts. In most countries, those with confirmed or suspected infections are requisitioned to isolate at home, putting other members of their household at risk of infection. Therefore, in parallel to the need of household transmission prevention measures, households also present as a good model for infection transmission studies, allowing for the testing of several close contact transmission prevention study hypotheses. Our hope is that if the trial results are encouraging, this will provide new and additional COVID-19 prevention strategies. Trial registration ISRCTN48554326 Registered on June 14, 2021