You-Lin Qiao1, Ting Wu2, Rong-Cheng Li3, Yue-Mei Hu4, Li-Hui Wei5, Chang-Gui Li6, Wen Chen1, Shou-Jie Huang2, Fang-Hui Zhao1, Ming-Qiang Li7, Qin-Jing Pan1, Xun Zhang1,8, Qing Li9, Ying Hong10, Chao Zhao5, Wen-Hua Zhang1, Yan-Ping Li3, Kai Chu4, Mei Li10, Yun-Fei Jiang10, Juan Li6, Hui Zhao6, Zhi-Jie Lin11, Xue-Lian Cui7, Wen-Yu Liu12, Cai-Hong Li8, Dong-Ping Guo13, Li-Dong Ke14, Xin Wu7, Jie Tang12, Guo-Qi Gao8, Ba-Yi Li13, Bin Zhao14, Feng-Xian Zheng8, Cui-Hong Dai14, Meng Guo2, Jun Zhao2, Ying-Ying Su2, Jun-Zhi Wang6, Feng-Cai Zhu4, Shao-Wei Li2, Hui-Rong Pan11, Yi-Min Li11, Jun Zhang2, Ning-Shao Xia2. 1. National Cancer Center, National Center for Cancer Clinical Research, The Cancer Institute, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. 2. The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen, Fujian, China. 3. Guangxi Center for Disease Control and Prevention, Nanning, Guangxi, China. 4. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China. 5. Peking University People's Hospital, Beijing, China. 6. National Institute for Food and Drug Control, Beijing, China. 7. Liuzhou Center for Disease Control and Prevention, Liuzhou, Guangxi, China. 8. Xinmi Maternal and Child Health Hospital, Xinmi, Henan, China. 9. Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, China. 10. The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. 11. Xiamen Innovax Biotech Company, Xiamen, Fujian, China. 12. Funing Center for Disease Control and Prevention, Funing, Jiangsu, China. 13. Yangcheng Maternal and Child Health Hospital, Yangcheng, Shanxi, China. 14. Fengning Hospital of Traditional Chinese Medicine, Fengning, Hebei, China.
Abstract
BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.
RCT Entities:
BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.
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Authors: Mélanie Drolet; Élodie Bénard; Marie-Claude Boily; Hammad Ali; Louise Baandrup; Heidi Bauer; Simon Beddows; Jacques Brisson; Julia M L Brotherton; Teresa Cummings; Basil Donovan; Christopher K Fairley; Elaine W Flagg; Anne M Johnson; Jessica A Kahn; Kimberley Kavanagh; Susanne K Kjaer; Erich V Kliewer; Philippe Lemieux-Mellouki; Lauri Markowitz; Aminata Mboup; David Mesher; Linda Niccolai; Jeannie Oliphant; Kevin G Pollock; Kate Soldan; Pam Sonnenberg; Sepehr N Tabrizi; Clare Tanton; Marc Brisson Journal: Lancet Infect Dis Date: 2015-03-03 Impact factor: 25.071
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