drugset / Trial / NCT04470427
A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19
Phase 3
Completed
30415 enrolled
ModernaTX, Inc.
Biomedical Advanced Research and Development Authority · collabNational Institute of Allergy and Infectious Diseases (NIAID) · collab
RandomizedParallel-groupQuadruple-blindPrevention
Summary
The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.
Timeline
- Start
- 2020-07-27
- Primary completion
- 2022-12-29
- Completion
- 2022-12-29
Outcome
Met primary endpoint
registry analysis (other test); Part A (Blinded): Placebo vs Part A (Blinded): mRNA-1273; p <.0001; VE 93.2 (95% CI 91.0 to 94.8); Vaccine Efficacy (VE) NCT04470427 ↗
release “Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study” q4web.com ↗
release “primary efficacy analysis of the Phase 3 study of mRNA-1273 conducted on 196 cases confirmed the high efficacy observed at the first interim analysis.” q4web.com ↗
release “639 cases of COVID-19 were observed in the placebo group versus 51 cases observed in the Moderna COVID-19 Vaccine group.” q4web.com ↗
release “Phase 3 COVE Study: Updated cases show continued strong efficacy, including greater than 90% against cases of COVID-19” q4web.com ↗
release “follow-up data from the Phase 3 COVE study showing high efficacy and favorable safety approximately six months after the second dose.” q4web.com ↗
Publications
- Kaplonek P, Bertera H, Lee DW, Cizmeci D, Yu WH, Wu K, Chalkias S, Wahid R, Edwards D, Alter G, Henry C. IgG4 Neutralization and Sustained Total IgG Fc-Effector Functions Following Repeated SARS-CoV-2 Vaccination with mRNA-1273. Infect Dis Ther. 2026 Mar;15(3):859-874. doi: 10.1007/s40121-026-01303-w. Epub 2026 Feb 1.
- Kenny A, van der Laan L, Gilbert P, Carone M. Inference on Controlled Effects for Assessing Immune Correlates of Protection Based on a Cox Model. Stat Med. 2025 Dec;44(28-30):e70347. doi: 10.1002/sim.70347.
- Ashby E, Janes H, Follmann D, Gilbert PB, Zhou H, Wang X, Girard B, Priddy F, Kublin JG, Corey L, Neuzil KM, Baden LR, El Sahly HM, Zhang B; COVE study group. Validating and leveraging non-SARS-CoV-2 respiratory infection as a negative control outcome in a phase 3 COVID-19 vaccine trial with extended observational follow-up. Am J Epidemiol. 2026 Jan 8;195(1):168-177. doi: 10.1093/aje/kwaf176.
- Follmann D, Wang X, Baden LR, El Sahly HM, Essink B, Gilbert P, Janes HE, Kelley CF, Berman MA, Frank I, Chu E, Deng W, Priddy F, Dixit A, Tomassini JE, Das R, Miller J, Zhou H. Who to Boost When: The Effect of Age and Dosing Interval on Delta and Omicron COVID-19 Incidence in the Open-label Phase of the COVE Trial. Open Forum Infect Dis. 2024 Nov 25;11(12):ofae689. doi: 10.1093/ofid/ofae689. eCollection 2024 Dec.
- Zhang B, Fong Y, Fintzi J, Chu E, Janes HE, Kenny A, Carone M, Benkeser D, van der Laan LWP, Deng W, Zhou H, Wang X, Lu Y, Yu C, Borate B, Chen H, Reeder I, Carpp LN, Houchens CR, Martins K, Jayashankar L, Huynh C, Fichtenbaum CJ, Kalams S, Gay CL, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Priddy F, Das R, Girard B, El Sahly HM, Baden LR, Jones T, Donis RO, Koup RA, Gilbert PB, Follmann D; United States Government (USG) COVID-19 Immune Assays Team; Moderna, Inc. Team; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team; USG/CoVPN Biostatistics Team. Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial. Nat Commun. 2024 Sep 11;15(1):7954. doi: 10.1038/s41467-024-52348-9.
- Janes H, Fisher LH, Kee JJ, Parameswaran L, Goepfert PA, Falsey AR, Ludwig J, Magaret CA, Gilbert PB, Kublin JG, Rouphael N, Sobieszczyk ME, El Sahly HM, Baden LR, Grinsztejn B, Walsh SR, Gray GE, Kotloff KL, Gay CL, Greninger AL, Tapia MD, Hammershaimb EA, Priddy FH, Green JA, Struyf F, Dunkle L, Neuzil KM, Corey L, Huang Y. Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials. J Infect Dis. 2024 Dec 16;230(6):1384-1389. doi: 10.1093/infdis/jiae400.
- Baden LR, El Sahly HM, Essink B, Follmann D, Hachigian G, Strout C, Overcash JS, Doblecki-Lewis S, Whitaker JA, Anderson EJ, Neuzil K, Corey L, Priddy F, Tomassini JE, Brown M, Girard B, Stolman D, Urdaneta V, Wang X, Deng W, Zhou H, Dixit A, Das R, Miller JM; COVE Trial Consortium. Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases. Nat Commun. 2024 Aug 29;15(1):7469. doi: 10.1038/s41467-024-50376-z.
- Turley CB, Tables L, Fuller T, Sanders LJ, Scott H, Moodley A, Woodward Davis A, Leav B, Miller J, Schoemaker K, Vandebosch A, Sadoff J, Woo W, Cho I, Dunkle LM, Li S, van der Laan L, Gilbert PB, Follmann D, Jaynes H, Kublin JG, Baden LR, Goepfert P, Kotloff K, Gay CL, Falsey AR, El Sahly HM, Sobieszczyk ME, Huang Y, Neuzil KM, Corey L, Grinsztejn B, Gray G, Rouphael N, Luedtke A; COVID-19 Prevention Network CoVPN. Modifiers of COVID-19 vaccine efficacy: Results from four COVID-19 prevention network efficacy trials. Vaccine. 2023 Jul 25;41(33):4899-4906. doi: 10.1016/j.vaccine.2023.06.066. Epub 2023 Jun 23.
- Follmann D, O'Brien MP, Fintzi J, Fay MP, Montefiori D, Mateja A, Herman GA, Hooper AT, Turner KC, Chan KC, Forleo-Neto E, Isa F, Baden LR, El Sahly HM, Janes H, Doria-Rose N, Miller J, Zhou H, Dang W, Benkeser D, Fong Y, Gilbert PB, Marovich M, Cohen MS. Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration. Nat Commun. 2023 Jun 17;14(1):3605. doi: 10.1038/s41467-023-39292-w.
- Benkeser D, Montefiori DC, McDermott AB, Fong Y, Janes HE, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O'Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Kenny A, Carone M, Williamson BD, Garver J, Altonen E, Rudge T, Huynh C, Miller J, El Sahly HM, Baden LR, Frey S, Malkin E, Spector SA, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA, Gilbert PB; Immune Assays; Moderna Inc.; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE); United States Government (USG)/CoVPN Biostatistics Teams. Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial. Sci Transl Med. 2023 Apr 19;15(692):eade9078. doi: 10.1126/scitranslmed.ade9078. Epub 2023 Apr 19.
- Chalkias S, Eder F, Essink B, Khetan S, Nestorova B, Feng J, Chen X, Chang Y, Zhou H, Montefiori D, Edwards DK, Girard B, Pajon R, Dutko FJ, Leav B, Walsh SR, Baden LR, Miller JM, Das R. Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. Nat Med. 2022 Nov;28(11):2388-2397. doi: 10.1038/s41591-022-02031-7. Epub 2022 Oct 6.
- Fraiman J, Erviti J, Jones M, Greenland S, Whelan P, Kaplan RM, Doshi P. Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine. 2022 Sep 22;40(40):5798-5805. doi: 10.1016/j.vaccine.2022.08.036. Epub 2022 Aug 31.
- Follmann D, Janes HE, Buhule OD, Zhou H, Girard B, Marks K, Kotloff K, Desjardins M, Corey L, Neuzil KM, Miller JM, El Sahly HM, Baden LR. Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial. Ann Intern Med. 2022 Sep;175(9):1258-1265. doi: 10.7326/M22-1300. Epub 2022 Jul 5.
- El Sahly HM, Baden LR, Essink B, Montefiori D, McDermont A, Rupp R, Lewis M, Swaminathan S, Griffin C, Fragoso V, Miller VE, Girard B, Paila YD, Deng W, Tomassini JE, Paris R, Schodel F, Das R, August A, Leav B, Miller JM, Zhou H, Pajon R; Coronavirus Efficacy (COVE) Study Group. Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 Coronavirus Efficacy (COVE) Trial. J Infect Dis. 2022 Nov 11;226(10):1731-1742. doi: 10.1093/infdis/jiac188.
- Pajon R, Paila YD, Girard B, Dixon G, Kacena K, Baden LR, El Sahly HM, Essink B, Mullane KM, Frank I, Denhan D, Kerwin E, Zhao X, Ding B, Deng W, Tomassini JE, Zhou H, Leav B, Schodel F; COVE Trial Consortium. Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial. Nat Med. 2022 Apr;28(4):823-830. doi: 10.1038/s41591-022-01679-5. Epub 2022 Feb 10.
- El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, Campbell TB, Clark J, Jackson LA, Fichtenbaum CJ, Zervos M, Rankin B, Eder F, Feldman G, Kennelly C, Han-Conrad L, Levin M, Neuzil KM, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Polakowski L, Mascola JR, Ledgerwood JE, Graham BS, August A, Clouting H, Deng W, Han S, Leav B, Manzo D, Pajon R, Schodel F, Tomassini JE, Zhou H, Miller J; COVE Study Group. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. N Engl J Med. 2021 Nov 4;385(19):1774-1785. doi: 10.1056/NEJMoa2113017. Epub 2021 Sep 22.
- Gilbert PB, Montefiori DC, McDermott A, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O'Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi N, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Kutner M, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA. Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial. medRxiv [Preprint]. 2021 Aug 15:2021.08.09.21261290. doi: 10.1101/2021.08.09.21261290.
- Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | mRNA-1273 | Messenger RNA (mRNA) | 50 ug | Intramuscular |
| Subject | mRNA-1273 | Messenger RNA (mRNA) | 100 ug | Intramuscular |