Randomised controlled phase I trial of a SARS‐CoV‐2 monoclonal antibody
13 affiliations
- 1Department of Microbiology and Immunology University of Melbourne, The Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia
- 2Faculty of Medicine and Health, Sydney School of Public Health The University of Sydney Sydney NSW Australia
- 3Department of Infectious Diseases University of Melbourne, The Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia
- 4Programme in Emerging Infectious Diseases Duke‐NUS Medical School Singapore Singapore
- 5Infectious Diseases Translational Research Program, Department of Microbiology and Immunology Yong Loo Lin School of Medicine, National University of Singapore Singapore Singapore
- 6National Centre for Infectious Diseases Singapore Singapore
- 7Nucleus Network Melbourne VIC Australia
- 8Department of Infectious Diseases The Alfred Hospital and School of Translational Medicine, Monash University Melbourne VIC Australia
- 9BioSensis Consulting Brisbane QLD Australia
- 10Biotherapeutics Program CSIRO Biosecurity Clayton VIC Australia
- 11Kirby Institute University of New South Wales Kensington NSW Australia
- 12National Biologics Facility, Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane QLD Australia
- 13Melbourne Sexual Health Centre and Department of Infectious Diseases Alfred Hospital and Central Clinical School, Monash University Melbourne VIC Australia
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.
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BibTeX
@article{lee2026randomised,
title = {{Randomised controlled phase I trial of a SARS‐CoV‐2 monoclonal antibody}},
author = {Wen Shi Lee and Kevin J Selva and Timothy E Schlub and Jennifer Audsley and Janavi S Rambhatla and Robyn Esterbauer and Jennifer A Juno and Andrew Kelly and Ellie Reilly and Thakshila Amarasena and Sarah Lee and Hyon‐Xhi Tan and Chee Wah Tan and Lin‐Fa Wang and Christina C Chang and Michael Gerometta and Judith A Scoble and Patrick F James and Arnold Reynaldi and Miles P Davenport and Kym Hoger and Karen Hughes and Martina L Jones and Ben Hughes and Adam K Wheatley and Stephen J Kent},
journal = {Clinical \& Translational Immunology},
year = {2026},
month = nov,
doi = {10.1002/cti2.70126},
url = {https://doi.org/10.1002/cti2.70126},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Randomised controlled phase I trial of a SARS‐CoV‐2 monoclonal antibody
AU - Wen Shi Lee
AU - Kevin J Selva
AU - Timothy E Schlub
AU - Jennifer Audsley
AU - Janavi S Rambhatla
AU - Robyn Esterbauer
AU - Jennifer A Juno
AU - Andrew Kelly
AU - Ellie Reilly
AU - Thakshila Amarasena
AU - Sarah Lee
AU - Hyon‐Xhi Tan
AU - Chee Wah Tan
AU - Lin‐Fa Wang
AU - Christina C Chang
AU - Michael Gerometta
AU - Judith A Scoble
AU - Patrick F James
AU - Arnold Reynaldi
AU - Miles P Davenport
AU - Kym Hoger
AU - Karen Hughes
AU - Martina L Jones
AU - Ben Hughes
AU - Adam K Wheatley
AU - Stephen J Kent
PY - 2026
DA - 2026/11/04
JO - Clinical & Translational Immunology
DO - 10.1002/cti2.70126
UR - https://doi.org/10.1002/cti2.70126
AB - 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.
SN - 2050-0068
ER -