BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is immunogenic, has a clinically acceptable safety profile, and prevents incident and persistent HPV-16/18 infection and cervical precancerous lesions. This study (NCT00552279) evaluated the vaccine when administered according to an alternative dosing schedule (0-1-12 months) compared with the standard dosing schedule (0-1-6 months). METHODS: The study was of randomized open design and was conducted at multiple centers in Europe. Healthy women aged 15 to 25 years were randomized (1:1) to receive HPV-16/18 vaccine according to the standard schedule at months 0, 1, and 6 (n = 401) or an alternative schedule at months 0, 1, and 12 (n = 403). HPV-16 and -18 antibodies were measured by enzyme-linked immunosorbent assay at months 0, 2, and 7 or 13 (depending on group); noninferiority evaluation was performed sequentially for seroconversion rates and geometric mean antibody titers. Primary analysis of immunogenicity was based on the according-to-protocol cohort. Vaccine safety and reactogenicity were assessed on the total vaccinated cohort. RESULTS: Predefined noninferiority criteria were met 1 month after the third vaccine dose when the HPV-16/18 vaccine was administered according to the 0-1-12 month schedule compared with the 0-1-6 month schedule in terms of seroconversion rates for HPV-16 (100% and 100%) and HPV-18 (99.7% and 100%) and geometric mean antibody titers for HPV-16 (11884.7 and 10311.9 ELISA units/mL) and HPV-18 (4501.3 and 3963.6 ELISA units/mL), respectively. The HPV-16/18 vaccine had a clinically acceptable safety profile when administered according to either schedule. CONCLUSIONS: The third dose of the HPV-16/18 vaccine can be administered any time between 6 and 12 months after the first dose, with adequate immunogenicity and a clinically acceptable safety profile.
RCT Entities:
BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is immunogenic, has a clinically acceptable safety profile, and prevents incident and persistent HPV-16/18 infection and cervical precancerous lesions. This study (NCT00552279) evaluated the vaccine when administered according to an alternative dosing schedule (0-1-12 months) compared with the standard dosing schedule (0-1-6 months). METHODS: The study was of randomized open design and was conducted at multiple centers in Europe. Healthy women aged 15 to 25 years were randomized (1:1) to receive HPV-16/18 vaccine according to the standard schedule at months 0, 1, and 6 (n = 401) or an alternative schedule at months 0, 1, and 12 (n = 403). HPV-16 and -18 antibodies were measured by enzyme-linked immunosorbent assay at months 0, 2, and 7 or 13 (depending on group); noninferiority evaluation was performed sequentially for seroconversion rates and geometric mean antibody titers. Primary analysis of immunogenicity was based on the according-to-protocol cohort. Vaccine safety and reactogenicity were assessed on the total vaccinated cohort. RESULTS: Predefined noninferiority criteria were met 1 month after the third vaccine dose when the HPV-16/18 vaccine was administered according to the 0-1-12 month schedule compared with the 0-1-6 month schedule in terms of seroconversion rates for HPV-16 (100% and 100%) and HPV-18 (99.7% and 100%) and geometric mean antibody titers for HPV-16 (11884.7 and 10311.9 ELISA units/mL) and HPV-18 (4501.3 and 3963.6 ELISA units/mL), respectively. The HPV-16/18 vaccine had a clinically acceptable safety profile when administered according to either schedule. CONCLUSIONS: The third dose of the HPV-16/18 vaccine can be administered any time between 6 and 12 months after the first dose, with adequate immunogenicity and a clinically acceptable safety profile.
Authors: G Gross; N Becker; N H Brockmeyer; S Esser; U Freitag; M Gebhardt; L Gissmann; P Hillemanns; H Grundhewer; H Ikenberg; H Jessen; A Kaufmann; S Klug; J P Klußmann; A Nast; D Pathirana; K U Petry; H Pfister; U Röllinghof; P Schneede; A Schneider; E Selka; S Singer; S Smola; B Sporbeck; M von Knebel Doeberitz; P Wutzler Journal: Geburtshilfe Frauenheilkd Date: 2014-03 Impact factor: 2.915
Authors: Hanna Bergman; Brian S Buckley; Gemma Villanueva; Jennifer Petkovic; Chantelle Garritty; Vittoria Lutje; Alina Ximena Riveros-Balta; Nicola Low; Nicholas Henschke Journal: Cochrane Database Syst Rev Date: 2019-11-22
Authors: Alex C D Salyer; Giuseppe Caruso; Karishma K Khetani; Lauren M Fox; Subbalakshmi S Malladi; Sunil A David Journal: PLoS One Date: 2016-02-26 Impact factor: 3.240
Authors: Pedro Luiz Spinelli Coelho; Gustavo Lacerda da Silva Calestini; Fernando Salgueiro Alvo; Jefferson Michel de Moura Freitas; Paula Marcela Vilela Castro; Tulio Konstantyner Journal: Rev Paul Pediatr Date: 2015-08-29
Authors: Chul-Jung Kim; Rok Song; Jing Chen; Fernanda Tavares Da Silva; Kusuma B Gopala; Joon Hyung Kim; Dan Bi; Jong Sup Park Journal: Pharmacoepidemiol Drug Saf Date: 2017-03-07 Impact factor: 2.890
Authors: Mallesh Beesu; Subbalakshmi S Malladi; Lauren M Fox; Cassandra D Jones; Anshuman Dixit; Sunil A David Journal: J Med Chem Date: 2014-08-20 Impact factor: 7.446