Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Objectives 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. Methods 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. Results 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. Conclusion Overall, the mAb PDI204 was safe but lost activity against later Omicron strains and did not prevent COVID‐19 during this trial.
DOI: 10.1002/cti2.70126
Authors: Wen Shi Lee, Kevin J Selva, Timothy E Schlub, Jennifer Audsley, Janavi S Rambhatla, Robyn Esterbauer, Jennifer A Juno, Andrew Kelly, Ellie Reilly, Thakshila Amarasena, Sarah Lee, Hyon‐Xhi Tan, Chee Wah Tan, Lin‐Fa Wang, Christina C Chang, Michael Gerometta, Judith A Scoble, Patrick F James, Arnold Reynaldi, Miles P Davenport, Kym Hoger, Karen Hughes, Martina L Jones, Ben Hughes, Adam K Wheatley, Stephen J Kent
Institutions: The University of Melbourne, Peter Doherty Institute, The University of Sydney, National University of Singapore, Duke-NUS Medical School, National Centre for Infectious Diseases, The Alfred Hospital, Monash University, CSIRO Health and Biosecurity, UNSW Sydney, Kirby Institute, The University of Queensland, Melbourne Sexual Health Centre
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,070
OpenAlex ID: W7225238474