Clinical Trial: Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: 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, A
Brief Summary:
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.
PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.
Detailed Summary:
OBJECTIVES:
Primary
•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.
Secondary
- 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.
- Number of Cervical Infection With HPV16 or HPV18. [ Time Frame: From Month 6 up to Month 48 ]Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type [ Time Frame: From Month 6 up to Month 48 ]
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen.
Note: The assay did not distinguish between HPV types 68 and 73.
CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases [ Time Frame: From Month 6 up to Month 48 ]
Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type.
Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months.
Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.
- Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]
Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs).
Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination.
Seropositive subjects=antibody concentration equal to or above 8 EL.U/mL prior to vaccination.
Immunogenicity subcohort = subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7)
- Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]
Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs).
Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination.
Seropositive (Sero+) subjects=antibody concentration equal to or above 7 EL.U/mL prior to vaccination.
Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).
- HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]
Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs).
Seronegative (Sero-) subjects=antibody concentration below 41 EL.U/mL prior to vaccination.
Seropositive (Sero+) subjects=antibody concentration equal to or above 41 EL.U/mL prior to vaccination.
Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).
- HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]
Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs).
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Original Secondary Outcome:
Information By: GlaxoSmithKline
Dates:
Date Received: August 8, 2005
Date Started: June 2004
Date Completion:
Last Updated: May 24, 2012
Last Verified: May 2012
Sponsor: GlaxoSmithKline
Current Primary Outcome: Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. [ Time Frame: From Month 6 up to Month 48 ]
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.
Original Primary Outcome:
Current Secondary Outcome:
