Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

被引：313

作者：

Dunkle, Lisa M. ^{[1
]}

Kotloff, Karen L. ^{[2
]}

Gay, Cynthia L. ^{[11
]}

Anez, German ^{[1
]}

Adelglass, Jeffrey M. ^{[2
,7
]}

Barrat Hernandez, Alejandro Q. ^{[5
]}

Harper, Wayne L. ^{[9
]}

Duncanson, Daniel M. ^{[12
]}

McArthur, Monica A.

Florescu, Diana F. ^{[14
]}

McClelland, R. Scott ^{[15
]}

Garcia-Fragoso, Veronica ^{[8
]}

Riesenberg, Robert A. ^{[18
]}

Musante, David B. ^{[10
]}

Fried, David L. ^{[20
]}

Safirstein, Beth E. ^{[13
]}

McKenzie, Mark ^{[21
]}

Jeanfreau, Robert J. ^{[22
]}

Kingsley, Jeffrey K. ^{[19
]}

Henderson, Jeffrey A. ^{[23
]}

Lane, Dakotah C. ^{[17
]}

Ruiz-Palacios, Guillermo M. ^{[6
]}

Corey, Lawrence ^{[16
]}

Neuzil, Kathleen M. ^{[2
]}

Coombs, Robert W. ^{[15
]}

Greninger, Alex L. ^{[15
]}

Hutter, Julia ^{[3
]}

Ake, Julie A. ^{[4
]}

Smith, Katherine ^{[1
]}

Woo, Wayne ^{[1
]}

Cho, Iksung ^{[1
]}

Glenn, Gregory M. ^{[1
]}

Dubovsky, Filip ^{[1
]}

机构：

[1] Novavax, 21 Firstfield Rd, Gaithersburg, MD 20878 USA

[2] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[3] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] Walter Reed Army Inst Res, Silver Spring, MD USA

[5] FAICIC Clin Res, Veracruz, Mexico

[6] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico

[7] Res Your Hlth, Plano, TX USA

[8] Texas Ctr Drug Dev, Houston, TX USA

[9] M3 Wake Res, Raleigh, NC USA

[10] M3 Emerging Med Res, Durham, NC USA

[11] Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA

[12] SIMEDHealth, Gainesville, FL USA

[13] Velocity Clin Res, Hallandale Beach, FL USA

[14] Univ Nebraska Med Ctr, Omaha, NE USA

[15] Univ Washington, Med Ctr, Seattle, WA 98195 USA

[16] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[17] Lummi Indian Hlth Ctr, Bellingham, WA USA

[18] Atlanta Ctr Med Res, Atlanta, GA USA

[19] IACT Hlth, Columbus, GA USA

[20] Velocity Clin Res Providence, Warwick, RI USA

[21] WR ClinSearch, Chattanooga, TN USA

[22] MedPharmics, Metairie, LA USA

[23] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 386卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1056/NEJMoa2116185

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (>= 18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% >= 65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains.

引用

页码：531 / 543

页数：13

共 24 条

[1]

[Anonymous], 2021, MYOCARDITIS PERICARD

[2]

[Anonymous], 2021, PEOPLE CERTAIN MEDIC

[3]

[Anonymous], 2021, Coronavirus (COVID-19) update: FDA authorizes additional oral antiviral for treatment of COVID-19 in certain adults

[4]

[Anonymous], 2020, GUIDANCE IND DEV LIC

[5]

[Anonymous], 2021, SARS-Cov-2 variant of concern and variants under investigation in England

[6] Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J].

Baden, Lindsey R. ;

El Sahly, Hana M. ;

Essink, Brandon ;

Kotloff, Karen ;

Frey, Sharon ;

Novak, Rick ;

Diemert, David ;

Spector, Stephen A. ;

Rouphael, Nadine ;

Creech, C. Buddy ;

McGettigan, John ;

Khetan, Shishir ;

Segall, Nathan ;

Solis, Joel ;

Brosz, Adam ;

Fierro, Carlos ;

Schwartz, Howard ;

Neuzil, Kathleen ;

Corey, Larry ;

Gilbert, Peter ;

Janes, Holly ;

Follmann, Dean ;

Marovich, Mary ;

Mascola, John ;

Polakowski, Laura ;

Ledgerwood, Julie ;

Graham, Barney S. ;

Bennett, Hamilton ;

Pajon, Rolando ;

Knightly, Conor ;

Leav, Brett ;

Deng, Weiping ;

Zhou, Honghong ;

Han, Shu ;

Ivarsson, Melanie ;

Miller, Jacqueline ;

Zaks, Tal .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (05) :403-416

[7]

Center for Biologics Evaluation and Research, 2007, GUID IND TOX GRAD SC

[8] A strategic approach to COVID-19 vaccine R&D [J].

Corey, Lawrence ;

Mascola, John R. ;

Fauci, Anthony S. ;

Collins, Francis S. .

SCIENCE, 2020, 368 (6494) :948-950

[9] Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine [J].

Falsey, Ann R. ;

Sobieszczyk, Magdalena E. ;

Hirsch, Ian ;

Sproule, Stephanie ;

Robb, Merlin L. ;

Corey, Lawrence ;

Neuzil, Kathleen M. ;

Hahn, William ;

Hunt, Julie ;

Mulligan, Mark J. ;

McEvoy, Charlene ;

DeJesus, Edwin ;

Hassman, Michael ;

Little, Susan J. ;

Pahud, Barbara A. ;

Durbin, Anna ;

Pickrell, Paul ;

Daar, Eric S. ;

Bush, Larry ;

Solis, Joel ;

Carr, Quito Osuna ;

Oyedele, Temitope ;

Buchbinder, Susan ;

Cowden, Jessica ;

Vargas, Sergio L. ;

Benavides, Alfredo Guerreros ;

Call, Robert ;

Keefer, Michael C. ;

Kirkpatrick, Beth D. ;

Pullman, John ;

Tong, Tina ;

Isaacs, Margaret Brewinski ;

Benkeser, David ;

Janes, Holly E. ;

Nason, Martha C. ;

Green, Justin A. ;

Kelly, Elizabeth J. ;

Maaske, Jill ;

Mueller, Nancy ;

Shoemaker, Kathryn ;

Takas, Therese ;

Marshall, Richard P. ;

Pangalos, Menelas N. ;

Villafana, Tonya ;

Gonzalez-Lopez, Antonio .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (25) :2348-2360

[10] A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated [J].

Follmann, Dean ;

Fintzi, Jonathan ;

Fay, Michael P. ;

Janes, Holly E. ;

Baden, Lindsey R. ;

El Sahly, Hana M. ;

Fleming, Thomas R. ;

Mehrotra, Devan, V ;

Carpp, Lindsay N. ;

Juraska, Michal ;

Benkeser, David ;

Donnell, Deborah ;

Fong, Youyi ;

Han, Shu ;

Hirsch, Ian ;

Huang, Ying ;

Huang, Yunda ;

Hyrien, Ollivier ;

Luedtke, Alex ;

Carone, Marco ;

Nason, Martha ;

Vandebosch, An ;

Zhou, Honghong ;

Cho, Iksung ;

Gabriel, Erin ;

Kublin, James G. ;

Cohen, Myron S. ;

Corey, Lawrence ;

Gilbert, Peter B. ;

Neuzil, Kathleen M. .

ANNALS OF INTERNAL MEDICINE, 2021, 174 (08) :1118-+

← 1 2 3 →