A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia (CIN2, CIN3, Adenocarcinoma In Situ [AIS] and Invasive Cervical Cancer) Associated With HPV 16 or HPV 18 Cervical Infection in Healthy Young Adult Women in Costa Rica.
•Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18)
L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3
cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive
cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger
healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the
corresponding HPV type at months 0 and 6.
- Determine the duration of protection against HPV 16 or HPV 18 cervical infection in
participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.
- Determine the safety of this vaccine in these participants, regardless of their initial
HPV 16/18 DNA status.
- Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared
with control in preventing CIN2+ associated with any oncogenic HPV type cervical
infection in participants who are negative for HPV DNA by PCR for the corresponding HPV
type at months 0 and 6.
- Compare the efficacy of the candidate vaccine with control in preventing CIN2+
associated with HPV 16 or HPV 18 cervical infection, detected within the lesional
component of the cervical tissue specimen by PCR, in participants who are negative for
HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked
immunosorbent assay (ELISA) at month 0.
- Compare the efficacy of the candidate vaccine with control in preventing persistent HPV
16 or HPV 18 cervical infection in these participants.
- Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4
monoclonal antibody inhibition enzyme immunoassay in the first 600 participants
randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.
OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants
are randomized to 1 of 2 treatment arms.
- Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04
vaccine intramuscularly (IM) once in months 0, 1, and 6.
- Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and
After completion of study treatment, participants are followed at 6 months and then at least
annually for 3 years.
PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.
From Month 6 up to Month 48
GSK Clinical Trials
United States: Food and Drug Administration