Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE).

Background: The prevention of coronavirus disease 2019 (COVID-19) 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.
Competing Interests: 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; and is a paid member of a DSMB for Adamis, AlloVir, CSL Seqirus, Merck, Takeda, and Talaris. All study investigators, including D.F.W. and M.D., were compensated by Invivyd, Inc., for all patient visits including enrollment/baseline and follow-up. A.H., A.P., Y.L., D.G., K.N., K.T., E.H., I.Y., E.C., P.H., and P.S. were employees of Invivyd, Inc., at the time the study was conducted and may hold stock or shares. L.E.C. was a paid consultant to Invivyd, Inc., at the time the study was conducted but did not receive any financial remuneration for work done reviewing the paper. All other authors report no potential conflicts.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)