Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate COVID-19: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron
Authors: Ison Michael G , Popejoy Myra , Evgeniev Nikolay , Tzekova Maria , Mahoney Kathryn , Betancourt Natalia , Li Yong , Gupta Deepali , Narayan Kristin , Hershberger Ellie , Connolly Lynn E , Yalcin Ilker , Das Anita F , Genge John , Smith Michelle , Campanaro Ed , Hawn Pamela , Schmidt Pete ,   for the STAMP Study Group, Muniz Heloísa Costa Ravagnani , Tzekova Maria , Palaveev Kiril , Tsenov Vasil , Pekova Lilia , Hadzhieva Antoaneta , Mitreva Roza , Nikolaev Nikolay , Gyuzeleva Elena , Kornmann Marc Oliver , Schmidt Olaf , Poulakou Garyfalia , Milionis Charalampos , Kofteridis Diamantis , Dimopoulos Meletios-Athanasios , Skopelitis Ilias , Kotanidou Anastasia , Tsiodras Sotirios , Kania Grzegorz , Grenik Dagmara , Zajac Tomasz , Streinu-Cercel Anca , Pillay-Ramaya Larisha , Mookadam Mohamed , Mohapi Lerato , Geldenhuys Johan George , Vahed Yacoob , Holmgren Chantelle , Mekebeb-Reuter Martha , Brumskine William , De Jong Douwe , Joseph Natasha , McHarry Kirsten , Wadvalla Shahid , Kobrynska Olena , Kireyev Igor , Lebed Kyrylo , Logoida Pavlo , Barna Olga , Gyrina Olga , Gundertaylo Bogdan , Rodionova Viktoriia 
Published: May 2023

Abstract

Background
Safe and effective treatments are needed to prevent severe outcomes in individuals with COVID-19. We report results from STAMP, a phase 2/3, multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended half-life monoclonal antibody, for treatment of high-risk ambulatory patients with mild to moderate COVID-19.

Methods
Non-hospitalized, unvaccinated participants aged ≥12 years with mild to moderate COVID-19 and ≥1 risk factor for disease progression were randomized to receive a single intramuscular injection of 300 mg adintrevimab or placebo. Enrollment was paused due to the global emergence of the Omicron BA.1/BA1.1 variants, against which adintrevimab showed reduced activity in vitro. The primary efficacy endpoint was COVID-19-related hospitalization or all-cause death through day 29 in participants with COVID-19 due to laboratory-confirmed or suspected non-Omicron SARS-CoV-2 variants.

Results
Between August 8, 2021, and January 11, 2022, 399 participants were randomized to receive adintrevimab (n=198) or placebo (n=201), including 336 with COVID-19 due to non-Omicron variants. COVID-19-related hospitalization or all-cause death through day 29 occurred in 8/169 (4.7%) participants in the adintrevimab group and 23/167 (13.8%) in the placebo group, a 66% relative risk reduction in favor of adintrevimab (standardized risk difference, -8.7% [95% CI, -14.71 to -2.67; P=.0047]). Incidence of treatment-emergent adverse events (TEAEs) was similar between treatment groups (33.9% for adintrevimab and 39.5% for placebo). No adintrevimab-related serious TEAEs were reported.

Conclusion
Treatment with a single intramuscular injection of adintrevimab provided protection against severe outcomes in high-risk ambulatory participants with COVID-19 due to susceptible variants, without safety concerns. Clinical Trial Registration. NCT04805671