Randomised controlled phase I trial of a SARS-CoV-2 monoclonal antibody

SARS-CoV-2 infection remains a threat to vulnerable groups. Neutralising monoclonal antibodies (mAbs) have shown efficacy in the treatment and prevention of COVID-19, but most mAbs have lost activity against recent Omicron strains.

We previously isolated a receptor binding domain-specific mAb from a COVID-19 convalescent donor, PDI204, which retained activity against several early Omicron strains. This randomised, double-blind, placebo-controlled phase I clinical trial enrolled healthy adults (n = 32) to receive PDI204 intravenously (IV) at three different doses (200, 600, 1200 mg) or intramuscularly (IM) at 300 mg.

PDI204 was safe and tolerable with only Grade 1 and 2 adverse events. High serum levels of PDI204 were detected in PDI204-dosed participants with a median elimination half-life of 17.7 days (IQR 16.3-22.1). Boosted neutralising activity and Fc receptor binding were observed in serum against ancestral and Omicron BA.5 SARS-CoV-2 strains, but not against the later Omicron strain XBB.1.5. IM-dosed subjects had peak PDI204 levels in serum 2-6 days later than IV-dosed subjects. Entry of PDI204 into saliva from blood was low and variable, and primarily detected in participants receiving 600 mg or 1200 mg doses. Three of 32 people acquired COVID-19 within 90 days of dosing, two receiving PDI204 and one in a placebo recipient.

Overall, the mAb PDI204 was safe but lost activity against later Omicron strains and did not prevent COVID-19 during this trial.