Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.
Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.
复制标题
DOI：
10.1056/nejmoa2117608
复制
发表时间：
2022-03-03
期刊：
影响因子：
--
通讯作者：
ENSEMBLE Study Group
中科院分区：
文献类型：
--
作者：
Sadoff J;Gray G;Vandebosch A;Cárdenas V;Shukarev G;Grinsztejn B;Goepfert PA;Truyers C;Van Dromme I;Spiessens B;Vingerhoets J;Custers J;Scheper G;Robb ML;Treanor J;Ryser MF;Barouch DH;Swann E;Marovich MA;Neuzil KM;Corey L;Stoddard J;Hardt K;Ruiz-Guiñazú J;Le Gars M;Schuitemaker H;Van Hoof J;Struyf F;Douoguih M;ENSEMBLE Study Group
在主要III期疗效分析中，Ad26.COV2.S疫苗对2019年重症冠状病毒病（Covid-19）、住院和死亡非常有效。我们在我们的多国、随机、安慰剂对照试验的双盲阶段进行了最终分析，在该试验中，成年人以1：1的比例被分配接受单剂量Ad26.COV2.S（5×1010个病毒颗粒）或安慰剂。主要终点是疫苗对符合方案人群中接种后至少14天和接种后至少28天发病的中度至重度重症Covid-19的有效性。还评估了安全性和关键次要和探索性终点。该分析的中位随访时间为4个月; 8940名参与者至少随访了6个月。符合方案人群中（39，185名参与者），接种后至少14天对中度至重度重症Covid-19的疫苗有效性为56.3%（95%置信区间[CI]，51.3 - 60.8;疫苗组484例vs安慰剂组1067例）;接种后至少28天，疫苗有效性为52.9%（95% CI，47.1 - 58.1;疫苗组433例vs安慰剂组883例）。在美国，主要针对参考菌株（B.1.D614G）和B.1.1.7（α）变体的有效性为69.7%（95% CI，60.7 - 76.9）;在其他地方，针对P.1（γ）、C.37（λ）和B.1.621（mu）变体的有效性降低。有效率为74.6%（95% CI，64.7至82.1）针对严重危重的Covid-19（仅4例由B.1.617.2 [delta]变异引起的重症病例），75.6%（95% CI，54.3至88.0）针对导致医疗干预的COVID-19（包括住院治疗），82.8%（95%CI，40.5至96.8）预防新冠肺炎相关死亡，保护持续6个月或更长时间。对任何严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的有效性为41.7%（95%CI，36.3至46.7）。Ad26.COV2.S主要与轻度至中度不良事件相关，未发现新的安全性问题。单剂量Ad26.COV2.S对中度至重度重症Covid-19的保护率为52.9%。保护因变量而异;观察到对严重Covid-19、医疗干预和死亡的保护高于对其他终点的保护，并持续6个月或更长时间。（由Janssen Research and Development等资助; ENSEMBLE ClinicalTrials.gov编号，NCT 04505722。）
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. 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. 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. 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.)