TY - JOUR
T1 - Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S
AU - Sadoff, J.
AU - Gray, G.
AU - Vandebosch, A.
AU - Cárdenas, V.
AU - Shukarev, G.
AU - Grinsztejn, B.
AU - Goepfert, P. A.
AU - Truyers, C.
AU - Van Dromme, I.
AU - Spiessens, B.
AU - Vingerhoets, J.
AU - Custers, J.
AU - Scheper, G.
AU - Robb, M. L.
AU - Treanor, J.
AU - Ryser, M. F.
AU - Barouch, D. H.
AU - Swann, E.
AU - Marovich, M. A.
AU - Neuzil, K. M.
AU - Corey, L.
AU - Stoddard, J.
AU - Hardt, K.
AU - Ruiz-Guiñazú, J.
AU - Le Gars, M.
AU - Schuitemaker, H.
AU - Van Hoof, J.
AU - Struyf, F.
AU - Douoguih, M.
N1 - Publisher Copyright:
© 2022 Massachusetts Medical Society.
PY - 2022/3/3
Y1 - 2022/3/3
N2 - BACKGROUND The Ad26.COV2.S vaccine was highly effective against severe critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. METHODS We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed. RESULTS Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe critical Covid-19 (with only 4 severe critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19 related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified. CONCLUSIONS A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.)
AB - BACKGROUND The Ad26.COV2.S vaccine was highly effective against severe critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. METHODS We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed. RESULTS Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe critical Covid-19 (with only 4 severe critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19 related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified. CONCLUSIONS A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.)
UR - https://www.scopus.com/pages/publications/85125680297
U2 - 10.1056/NEJMoa2117608
DO - 10.1056/NEJMoa2117608
M3 - Article
C2 - 35139271
AN - SCOPUS:85125680297
SN - 0028-4793
VL - 386
SP - 847
EP - 860
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 9
ER -