Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE)
Michael G Ison, Debra F Weinstein, Marta Dobryanska, Anna Holmes, Anne-Marie Phelan, Yong Li, Deepali Gupta, Kristin Narayan, Kazima Tosh, Ellie Hershberger, Lynn E Connolly, Ilker Yalcin, Ed Campanaro, Pamela Hawn, MD Pete Schmidt
Open Forum Infectious Diseases, doi:10.1093/ofid/ofad314
Background. The prevention of coronavirus disease 2019 in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended-half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19. Methods. Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo. Primary efficacy end points were reverse transcription polymerase chain reaction (RT-PCR)confirmed symptomatic COVID-19 through day 28 in the PEP cohort (RT-PCR-negative at baseline) and through month 3 in the PrEP cohort (RT-PCR-negative and seronegative at baseline) among participants randomized before emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant (November 30, 2021). Safety was assessed through 6 months. Results. Between April 27, 2021, and January 11, 2022, 2582 participants were randomized. In the primary efficacy analysis, RT-PCR-confirmed symptomatic COVID-19 occurred in 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab-and placebo-treated PEP participants, respectively (74.9% relative risk reduction [RRR]; standardized risk difference, -5.0%; 95% CI, -8.87% to -1.08%; P = .0123) and in 12/752 (1.6%) vs 40/728 (5.5%) adintrevimab-and placebo-treated PrEP participants, respectively (71.0% RRR; standardized risk difference, -3.9%; 95% CI, -5.75% to -2.01%; P < .0001). In a prespecified exploratory analysis of 428 PrEP participants randomized after the emergence of Omicron, adintrevimab reduced RT-PCR-confirmed symptomatic COVID-19 by 40.6% (standardized risk difference -8.4%; 95% CI, -15.35% to -1.46%; nominal P = .0177) vs placebo. Adintrevimab was well tolerated, with no serious drug-related adverse events reported. Conclusions. A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns. Clinical trial registration. NCT04859517.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Author contributions. L.E.C., A.H., A.P., and K.N. contributed to study design. L.E.C., A.H., A.P., and K.N. were involved in protocol development. D.W. and M.D. were principal investigators. P.S. provided oversight and leadership responsibility for the research activity planning and execution. A.H. and P.S. were responsible for medical monitoring. All authors contributed to data interpretation and were involved in drafting and critically revising the manuscript, and all authors approved the final version and are accountable for the accuracy and integrity of the manuscript. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication. Y.L. and D.G. verified the data. Financial support. This work was supported by Invivyd, Inc. (formerly Adagio Therapeutics, Inc.). Potential conflicts of interest. At the time of the study, M.G.I. received research support, paid to Northwestern University, from GlaxoSmithKline; received payment for consultation from ADMA Biologics, AlloVir, Atea, Cidara, Genentech, Invivyd, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins; received royalties from UpToDate;..
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' <jats:title>Methods</jats:title>\n'
' <jats:p>Eligible participants (vaccine-naïve, aged ≥12 years) were '
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' <jats:title>Results</jats:title>\n'
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' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>A single intramuscular injection of adintrevimab provided '
'prophylactic efficacy against COVID-19 due to susceptible variants without safety '
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' </jats:sec>',
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