COV-CHIM01: SARS-CoV-2 (COVID-19) Dose Finding Infection Study

This is a phase I dose escalation challenge study in which increasing titres of wild-type SARS-CoV-2 (1x10\^1 TCID\_50, 1x10\^2TCID\_50, 1x10\^3TCID\_50, 1x10\^4TCID\_50 and 1x10\^5TCID\_50) will be administered intranasally to different groups of volunteers in order to achieve a 50% (+/-10%) attack rate as determined by quantitative live viral detection and/or qPCR detection in naso-pharyngeal secretions at two consecutive 12 hourly time points (at least 24 hours after inoculation). Dose escalation will be capped at 10\^5 TCID50 and we will proceed to dose confirmation, following DSMB safety review, even if we do not meet our target attack rate of 50% +/- 10%, to enable a larger sample size to assess the dynamic range of protection at that dose and ensure confidence in the negative infection rate at that dose. A Data Safety Monitoring Board (DSMB) will review safety and quantitative virology at each dose level and will recommend continuation based on emergent data. Rescue treatment with a single course of oral Paxlovid will commence immediately after any warning symptoms or signs of COVID-19 disease beyond mild disease. Once the optimal dose of wildtype SARS-CoV-2 has been identified for previously infected volunteers and uninfected vaccinated volunteers (dose escalation groups 1 and 3), further challenge infections in groups 2 and 4 may proceed. Volunteers will remain in isolation rooms within the clinical trials unit for a minimum of 14 days post inoculation and until demonstration of the absence of live virus in two sequential samples. All 4 groups will together enrol up to 132 volunteers. This study will be funded by the Wellcome Trust and Department of Health and Social Care (DHSC).