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
Michael G. Ison, Myra W. Popejoy, Nikolay Evgeniev, M. Tzekova, Kathryn Mahoney, Natalia Betancourt, Yong Li, Deepali Gupta, Kristin Narayan, Ellie Hershberger, Lynn Connolly, Ilker Yalcin, Anita Das, John Genge, Michelle Smith, Ed Campanaro, Pamela Hawn, Peter Schmidt, for the STAMP Study Group, Heloísa Costa Ravagnani Muniz, M. Tzekova, Kiril R. Palaveev, Vasil Tsenov, Lilia Pekova, Antoaneta Hadzhieva, R. Mitreva, Н. А. Николаев, Elena Gyuzeleva, Marc Oliver Kornmann, Olaf Schmidt, Garyfalia Poulakou, Haralampos Milionis, Diamantis P. Kofteridis, Meletios Α. Dimopoulos, Ilias Skopelitis, Αnastasia Kotanidou, Sotirios Tsiodras, Grzegorz Kania, Dagmara Grenik, Tomasz Zając, Anca Streinu-Cercel, Larisha Pillay-Ramaya, Mohamed Mookadam, Lerato Mohapi, Johan Geldenhuys, Yacoob Vahed, Chantelle Holmgren, Martha Mekebeb-Reuter, William Brumskine, Douwe De Jong, Natasha Joseph, Kirsten McHarry, Shahid Wadvalla, Olena Kobrynska, I. V. Kireyev, Kyrylo Lebed, Pavlo Logoida, Ольга Василівна Барна, Olga Gyrina, Bogdan Gundertaylo, В. В. Родіонова
Abstract
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