PMID- 30638797 OWN - NLM STAT- MEDLINE DCOM- 20200707 LR - 20221207 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 37 IP - 6 DP - 2019 Feb 4 TI - Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up. PG - 889-897 LID - S0264-410X(18)31703-1 [pii] LID - 10.1016/j.vaccine.2018.12.030 [doi] AB - BACKGROUND: A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90 months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20-45 years of age. METHODS: Participants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15 days following each vaccination. Serious AEs (SAEs), pregnancy outcomes, new medical conditions, and fetal/infant SAEs were collected during the entire study. RESULTS: Of 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15 days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAEs in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAEs, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges. CONCLUSION: The qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20-45 years of age, consistent with findings from global trials and safety surveillance studies. TRIAL REGISTRATION: clinicaltrials.gov; NCT00834106. CI - Copyright (c) 2018. Published by Elsevier Ltd. FAU - Chen, Wen AU - Chen W AD - Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing, 100021, China. Electronic address: chenwen@cicams.ac.cn. FAU - Zhao, Yun AU - Zhao Y AD - Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China. FAU - Xie, Xing AU - Xie X AD - Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, China. Electronic address: xiex@zju.edu.cn. FAU - Liu, Jihong AU - Liu J AD - Department of Gynecologic Oncology, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou 510060, China. Electronic address: liujh@sysucc.org.cn. FAU - Li, Jingran AU - Li J AD - Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China. FAU - Zhao, Chao AU - Zhao C AD - Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China. FAU - Wang, Shaoming AU - Wang S AD - Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing, 100021, China. Electronic address: wangshaoming@cicams.ac.cn. FAU - Liao, Xueyan AU - Liao X AD - MSD R&D (China), 21 Rongda Road, Wangjing R&D Base, Zhongguancun Electronic Zone West Zone, Chaoyang District, Beijing 100012, China. Electronic address: Xue.yan.liao@merck.com. FAU - Shou, Qiong AU - Shou Q AD - MSD R&D (China), 21 Rongda Road, Wangjing R&D Base, Zhongguancun Electronic Zone West Zone, Chaoyang District, Beijing 100012, China. Electronic address: qiong.shou@merck.com. FAU - Zheng, Minghuan AU - Zheng M AD - MSD R&D (China), 21 Rongda Road, Wangjing R&D Base, Zhongguancun Electronic Zone West Zone, Chaoyang District, Beijing 100012, China. Electronic address: Ming.huan.zheng@merck.com. FAU - Saah, Alfred J AU - Saah AJ AD - Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: alfred_saah@merck.com. FAU - Wei, Lihui AU - Wei L AD - Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China. Electronic address: weilhpku@163.com. FAU - Qiao, Youlin AU - Qiao Y AD - Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing, 100021, China. Electronic address: qiaoy@cicams.ac.cn. LA - eng SI - ClinicalTrials.gov/NCT00834106 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190109 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18) SB - IM MH - Adult MH - Antibodies, Viral/*blood MH - Asian People MH - China MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/*administration & dosage/immunology MH - Humans MH - Middle Aged MH - Papillomavirus Infections/*prevention & control MH - Vaccination/adverse effects/statistics & numerical data MH - Vaccine Potency MH - Young Adult OTO - NOTNLM OT - Quadrivalent human papillomavirus vaccine OT - Randomised controlled trial OT - Safety EDAT- 2019/01/15 06:00 MHDA- 2020/07/08 06:00 CRDT- 2019/01/15 06:00 PHST- 2018/08/08 00:00 [received] PHST- 2018/11/26 00:00 [revised] PHST- 2018/12/14 00:00 [accepted] PHST- 2019/01/15 06:00 [pubmed] PHST- 2020/07/08 06:00 [medline] PHST- 2019/01/15 06:00 [entrez] AID - S0264-410X(18)31703-1 [pii] AID - 10.1016/j.vaccine.2018.12.030 [doi] PST - ppublish SO - Vaccine. 2019 Feb 4;37(6):889-897. doi: 10.1016/j.vaccine.2018.12.030. Epub 2019 Jan 9.