OpenLB
Open Library of Bioscience
Advanced Search
The New England journal of medicine
06 09, 2022;386 (23): 2188-2200.

Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

Myron J Levin, Andrew Ustianowski, Stéphane De Wit, Odile Launay, Miles Avila, Alison Templeton, Yuan Yuan, Seth Seegobin, Adam Ellery, Dennis J Levinson, Philip Ambery, Rosalinda H Arends, Rohini Beavon, Kanika Dey, Pedro Garbes, Elizabeth J Kelly, Gavin C K W Koh, Karen A Near, Kelly W Padilla, Konstantina Psachoulia, Audrey Sharbaugh, Katie Streicher, Menelas N Pangalos, Mark T Esser, PROVENT Study Group
Author Information
  1. Myron J Levin: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  2. Andrew Ustianowski: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  3. Stéphane De Wit: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  4. Odile Launay: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  5. Miles Avila: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  6. Alison Templeton: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  7. Yuan Yuan: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  8. Seth Seegobin: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  9. Adam Ellery: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  10. Dennis J Levinson: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  11. Philip Ambery: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  12. Rosalinda H Arends: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  13. Rohini Beavon: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  14. Kanika Dey: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  15. Pedro Garbes: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  16. Elizabeth J Kelly: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  17. Gavin C K W Koh: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  18. Karen A Near: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  19. Kelly W Padilla: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  20. Konstantina Psachoulia: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  21. Audrey Sharbaugh: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  22. Katie Streicher: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  23. Menelas N Pangalos: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
  24. Mark T Esser: From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
PMID: 35443106 DOI: 10.1056/NEJMoa2116620

Abstract

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.
METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.
RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group.
CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

Associated Data

ClinicalTrials.gov | NCT04625725

References

  1. Nat Med. 2021 Aug;27(8):1370-1378 [PMID: 34108716]
  2. Nat Med. 2020 Sep;26(9):1422-1427 [PMID: 32651581]
  3. MMWR Morb Mortal Wkly Rep. 2020 May 08;69(18): [PMID: 32379731]
  4. Nat Rev Immunol. 2021 Jun;21(6):382-393 [PMID: 33875867]
  5. Clin Microbiol Infect. 2019 Jan;25(1):60-64 [PMID: 29715552]
  6. Sci Transl Med. 2022 Mar 9;14(635):eabl8124 [PMID: 35076282]
  7. Open Forum Infect Dis. 2021 Jun 30;8(7):ofab353 [PMID: 34337100]
  8. Ann Rheum Dis. 2021 Oct;80(10):1339-1344 [PMID: 34035003]
  9. Nat Med. 2021 Oct;27(10):1744-1751 [PMID: 34331051]
  10. Am J Epidemiol. 2004 Apr 1;159(7):702-6 [PMID: 15033648]
  11. Nat Med. 2022 Mar;28(3):490-495 [PMID: 35046573]
  12. Antimicrob Agents Chemother. 2013 Dec;57(12):6147-53 [PMID: 24080653]
  13. N Engl J Med. 2021 Sep 23;385(13):1184-1195 [PMID: 34347950]
  14. Nat Microbiol. 2022 Mar;7(3):379-385 [PMID: 35132198]
  15. JAMA. 2021 Jul 6;326(1):46-55 [PMID: 34081073]
  16. Acta Crystallogr D Biol Crystallogr. 2008 Jun;64(Pt 6):700-4 [PMID: 18560159]
  17. N Engl J Med. 2021 Aug 12;385(7):661-662 [PMID: 34161700]
  18. Cell. 2022 Feb 3;185(3):467-484.e15 [PMID: 35081335]
  19. Clin Infect Dis. 2021 Feb 16;72(4):703-706 [PMID: 32562416]
  20. Nature. 2022 Apr;604(7906):553-556 [PMID: 35240676]
  21. Nature. 2020 Aug;584(7821):443-449 [PMID: 32668443]
  22. Science. 2022 Apr 22;376(6591):eabn8897 [PMID: 35324257]
  23. Lancet Respir Med. 2020 Jun;8(6):547-548 [PMID: 32401711]
  24. Vaccines (Basel). 2021 Jun 30;9(7): [PMID: 34208884]
  25. Nat Microbiol. 2021 Oct;6(10):1233-1244 [PMID: 34548634]
  26. BMJ. 2021 May 13;373:n1088 [PMID: 33985964]
  27. N Engl J Med. 2021 Oct 14;385(16):1474-1484 [PMID: 34320281]
  28. Gut. 2021 Oct;70(10):1884-1893 [PMID: 33903149]
  29. Lancet. 2021 May 15;397(10287):1819-1829 [PMID: 33964222]
  30. Lancet Reg Health Eur. 2021 Mar;2:100015 [PMID: 33870245]

Grants

  1. W911QY-21-9-0001/U.S. Department of Health and Human Services
  2. W911QY-21-9-0001/U.S. Department of Defense

MeSH Term

Adult
Antibodies, Monoclonal
Antibodies, Neutralizing
Antiviral Agents
COVID-19
Double-Blind Method
Drug Combinations
Humans
Injections, Intramuscular
SARS-CoV-2

Chemicals

Antibodies, Monoclonal
Antibodies, Neutralizing
Antiviral Agents
Drug Combinations
cilgavimab and tixagevimab drug combination
tixagevimab
cilgavimab
Clinical Trial, Phase III Journal Article Randomized Controlled Trial
Article has an altmetric score of 1595

Word Cloud

Created with Highcharts 10.0.0AZD7442placebogroupCovid-19participantsriskdoseprimarytwoSARS-CoV-2extendedsingleone0tixagevimabcilgavimabseverecoronavirushalf-life90daysincreasedcontaining183analysissafetyendpointadverseefficacytotal2%occurred8relativereduction95%BACKGROUND:monoclonal-antibodycombinationcomposedneutralizingantibodiesacuterespiratorysyndrome2shownprophylactictherapeuticeffectsanimalmodelsPharmacokineticdatahumansindicateapproximatelyMETHODS:ongoingphase3trialenrolledadults≥18yearsageinadequateresponsevaccinationdisease2019exposureParticipantsrandomlyassigned2:1ratioreceiveconsecutiveintramuscularinjectionseither300mgsalinefollowedincidenceeventssymptomaticinfectionconfirmedmeansreverse-transcriptase-polymerase-chain-reactionassayoccurringadministrationdayRESULTS:5197underwentrandomizationreceived34601737conducted30%becomeawarerandomizedassignment12213461353%593173634reportedleasteventmildmoderateseveritySymptomatic344117173110%767%confidenceinterval[CI]46P<0001follow-upmedian6monthsshowed828%CI65914FivecasescriticalCovid-19-relateddeathsCONCLUSIONS:preventionwithoutevidentconcernsFundedAstraZenecaUSgovernmentPROVENTClinicalTrialsgovnumberNCT04625725IntramuscularTixagevimab-CilgavimabPrevention

Similar Articles

Cited By