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; Pete Schmidt; EVADE Study Group

doi:10.1093/ofid/ofad314

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

Open Forum Infect Dis. 2023 Jun 13;10(7):ofad314. doi: 10.1093/ofid/ofad314. eCollection 2023 Jul.

Authors

Affiliations

¹ Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
² Science 37 Inc., Culver City, California, USA.
³ Department of Emergency Care and ARENSIA Exploratory Medicine, Kyiv City Clinical Hospital No. 12, Kyiv, Ukraine.
⁴ Invivyd, Inc., Waltham, Massachusetts, USA.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; adintrevimab; monoclonal antibody; prevention.

Associated data

ClinicalTrials.gov/NCT04859517