학술논문
Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials.
Document Type
Academic Journal
Author
Levin MJ; University of Colorado School of Medicine, Aurora, CO, USA.; Ustianowski A; North Manchester General Hospital, Manchester, UK.; De Wit S; Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.; Beavon R; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D, Cambridge, UK.; Thissen J; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D, Cambridge, UK.; Seegobin S; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D, Cambridge, UK.; Dey K; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D1 Medimmune Way, Gaithersburg, MD, 20878, USA.; Near KA; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D1 Medimmune Way, Gaithersburg, MD, 20878, USA.; Streicher K; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D1 Medimmune Way, Gaithersburg, MD, 20878, USA.; Kiazand A; Patient Safety, Chief Medical Office, R&D and Vaccines and Immune Therapies, AstraZeneca, Gaithersburg, MD, USA.; Esser MT; Vaccines and Immune Therapies, AstraZeneca, BioPharmaceuticals R&D1 Medimmune Way, Gaithersburg, MD, 20878, USA. mark.esser@astrazeneca.com.
Source
Publisher: Adis Country of Publication: New Zealand NLM ID: 101634499 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2193-8229 (Print) Linking ISSN: 21936382 NLM ISO Abbreviation: Infect Dis Ther Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2193-8229
Abstract
Introduction: The phase 3 PROVENT and STORM CHASER studies evaluated AZD7442 (tixagevimab/cilgavimab) for pre-exposure and post-exposure prophylaxis of symptomatic coronavirus disease 2019 (COVID-19). We report the final 15-month results of both studies.
Methods: In PROVENT, participants were randomized 2:1 to receive 300 mg AZD7442 (n = 3460) or placebo (n = 1737). In STORM CHASER, participants were enrolled within 8 days of exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individual and randomized 2:1 to receive 300 mg AZD7442 (n = 749) or placebo (n = 372).
Results: In PROVENT, the relative risk reduction (RRR) in symptomatic COVID-19 for AZD7442 versus placebo was 76.7% at primary analysis [95% confidence interval (CI) 46.1, 90.0; p < 0.001], 83.0% at day 183 (95% CI 67.3, 91.2; nominal p < 0.001), and 46.3% at day 366 (95% CI 23.1, 62.4; nominal p < 0.001). Severe/critical COVID-19 was reduced by 91.4% with AZD7442 versus placebo by day 366 (95% CI 61.3, 98.1; nominal p < 0.0001). Adverse events (AEs) occurred in 58.2% and 58.0% of participants administered AZD7442 or placebo, respectively; serious AEs (SAEs) occurred in 6.2% and 5.6%, respectively. In STORM CHASER, the RRR in symptomatic COVID-19 for AZD7442 versus placebo was 33.3% at primary analysis (95% CI - 25.9, 64.7; p = 0.212), 43.3% at day 183 (95% CI 1.4, 67.4; nominal p = 0.044) and 3.4% at day 366 (95% CI - 35.6, 31.2; nominal p = 0.842). Severe/critical COVID-19 did not occur in participants receiving AZD7442 versus 0.5% of participants receiving placebo by day 366. AEs occurred in 46.5% and 51.9% of participants administered AZD7442 or placebo, respectively; SAEs occurred in 2.7% and 4.3%, respectively. In both studies, serum concentration-time profiles over 457 days were similar for tixagevimab and cilgavimab and consistent with the extended half-life reported for AZD7442 (approximately 90 days).
Conclusion: This analysis provides proof of concept supporting long-term safety of intramuscularly administered AZD7442 for prevention of symptomatic/severe COVID-19. A graphical abstract is available with this article.
Gov Identifiers: PROVENT (NCT04625725) and STORM CHASER (NCT04625972).
(© 2024. The Author(s).)
Methods: In PROVENT, participants were randomized 2:1 to receive 300 mg AZD7442 (n = 3460) or placebo (n = 1737). In STORM CHASER, participants were enrolled within 8 days of exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individual and randomized 2:1 to receive 300 mg AZD7442 (n = 749) or placebo (n = 372).
Results: In PROVENT, the relative risk reduction (RRR) in symptomatic COVID-19 for AZD7442 versus placebo was 76.7% at primary analysis [95% confidence interval (CI) 46.1, 90.0; p < 0.001], 83.0% at day 183 (95% CI 67.3, 91.2; nominal p < 0.001), and 46.3% at day 366 (95% CI 23.1, 62.4; nominal p < 0.001). Severe/critical COVID-19 was reduced by 91.4% with AZD7442 versus placebo by day 366 (95% CI 61.3, 98.1; nominal p < 0.0001). Adverse events (AEs) occurred in 58.2% and 58.0% of participants administered AZD7442 or placebo, respectively; serious AEs (SAEs) occurred in 6.2% and 5.6%, respectively. In STORM CHASER, the RRR in symptomatic COVID-19 for AZD7442 versus placebo was 33.3% at primary analysis (95% CI - 25.9, 64.7; p = 0.212), 43.3% at day 183 (95% CI 1.4, 67.4; nominal p = 0.044) and 3.4% at day 366 (95% CI - 35.6, 31.2; nominal p = 0.842). Severe/critical COVID-19 did not occur in participants receiving AZD7442 versus 0.5% of participants receiving placebo by day 366. AEs occurred in 46.5% and 51.9% of participants administered AZD7442 or placebo, respectively; SAEs occurred in 2.7% and 4.3%, respectively. In both studies, serum concentration-time profiles over 457 days were similar for tixagevimab and cilgavimab and consistent with the extended half-life reported for AZD7442 (approximately 90 days).
Conclusion: This analysis provides proof of concept supporting long-term safety of intramuscularly administered AZD7442 for prevention of symptomatic/severe COVID-19. A graphical abstract is available with this article.
Gov Identifiers: PROVENT (NCT04625725) and STORM CHASER (NCT04625972).
(© 2024. The Author(s).)