Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate Coronavirus Disease 2019: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron

Michael G Ison; Myra Popejoy; Nikolay Evgeniev; Maria Tzekova; Kathryn Mahoney; Natalia Betancourt; Yong Li; Deepali Gupta; Kristin Narayan; Ellie Hershberger; Lynn E Connolly; Ilker Yalcin; Anita F Das; John Genge; Michelle Smith; Ed Campanaro; Pamela Hawn; Pete Schmidt; STAMP Study Group

doi:10.1093/ofid/ofad279

Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate Coronavirus Disease 2019: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron

Open Forum Infect Dis. 2023 May 24;10(6):ofad279. doi: 10.1093/ofid/ofad279. eCollection 2023 Jun.

Authors

Michael G Ison¹, Myra Popejoy², Nikolay Evgeniev³, Maria Tzekova⁴, Kathryn Mahoney², Natalia Betancourt², Yong Li², Deepali Gupta², Kristin Narayan², Ellie Hershberger², Lynn E Connolly², Ilker Yalcin², Anita F Das², John Genge², Michelle Smith², Ed Campanaro², Pamela Hawn², Pete Schmidt²; STAMP Study Group

Collaborators

STAMP Study Group:
Heloísa Costa Ravagnani Muniz, Maria Tzekova, Kiril Palaveev, Vasil Tsenov, Lilia Pekova, Antoaneta Hadzhieva, Roza Mitreva, Nikolay Nikolaev, Elena Gyuzeleva, Marc Oliver Kornmann, Olaf Schmidt, Garyfalia Poulakou, Charalampos Milionis, Diamantis Kofteridis, Meletios-Athanasios Dimopoulos, Ilias Skopelitis, Anastasia Kotanidou, Sotirios Tsiodras, Grzegorz Kania, Dagmara Grenik, Tomasz Zajac, Anca Streinu-Cercel, Larisha Pillay-Ramaya, Mohamed Mookadam, Lerato Mohapi, Johan George Geldenhuys, Yacoob Vahed, Chantelle Holmgren, Martha Mekebeb-Reuter, William Brumskine, Douwe De Jong, Natasha Joseph, Kirsten McHarry, Shahid Wadvalla, Olena Kobrynska, Igor Kireyev, Kyrylo Lebed, Pavlo Logoida, Olga Barna, Olga Gyrina, Bogdan Gundertaylo, Viktoriia Rodionova

Affiliations

¹ Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
² Invivyd, Inc, Waltham, Massachusetts, USA.
³ Complex Oncological Center, Ruse Pltd, Ruse, Bulgaria.
⁴ Department of Propedeutics of Internal Diseases, Medical University, Pleven, Bulgaria.

Abstract

Background: Safe and effective treatments are needed to prevent severe outcomes in individuals with coronavirus disease 2019 (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: Nonhospitalized, 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 severe acute respiratory syndrome coronavirus 2 variants.

Results: Between 8 August 2021 and 11 January 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 of 169 (4.7%) participants in the adintrevimab group and 23 of 167 (13.8%) participants in the placebo group, a 66% relative risk reduction in favor of adintrevimab (standardized risk difference, -8.7% [95% confidence interval, -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.

Conclusions: 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.

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

Associated data

ClinicalTrials.gov/NCT04805671