A Phase III, Double-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy of GlaxoSmithKline Biologicals. HPV-16/18 VLP AS04 Vaccine Compared to Hepatitis A Vaccine as Control in Prevention of Persistent HPV-16 or HPV-18 Cervical Infection and Cervical Neoplasia, Administered Intramuscularly According to a 0, 1, 6 Month Schedule in Healthy Females 15-25 Years of Age.
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Infections, Papillomavirus
- Sponsor
- GlaxoSmithKline
- Enrollment
- 18729
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
Human Papilloma virus (HPV) are viruses that cause a common infection of the skin and genitals in men and women. Several types of HPV infection are transmitted by sexual activity and, in women, can infect the cervix (part of the uterus or womb). This infection often goes away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. If a woman is not infected by HPV, it is very unlikely that she will get cervical cancer. This study will evaluate the efficacy of GSK Biologicals HPV 16/18 VLP/AS04 vaccine to prevent infection associated cervical pre-cancer and vaccine with HPV 16 or 18 and the vaccine safety, over 48 months, in young adolescents and women of 15/25 years of age at study start. Approximately 18.000 study subjects will either receive the HPV vaccine or a control vaccine (hepatitis A vaccine) administered intramuscularly according to a 0-1-6 month schedule.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed Description
NOTE: Some 178 centers participate in this study. Given that the recruitment is completed, the researchers have listed one center per country in this website. If required, further details of centers available on request.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A woman whom the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
- •A woman between, and including, 15 and 25 years of age at the time of the first vaccination.
- •Written informed consent must be obtained from the subject prior to enrollment (for subjects below the legal age of consent, written informed consent must be obtained from a parent or legal guardian of the subject and, in addition, the subject should sign and personally date a written informed assent).
- •Subject must be free of obvious health problems as established by medical history and clinical examination before entering into the study.
- •Subject must have a negative urine pregnancy test.
- •Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using adequate contraceptive precautions for 30 days prior to the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.
- •Has had no more than 6 lifetime sexual partners prior to enrollment. This criterion may not be applicable in subjects less than 18 years of age, according to local regulatory/ethical requirements.
- •Subject must have intact cervix.
Exclusion Criteria
- •Pregnant or breastfeeding. Women must be at least 3 months post-pregnancy and not breastfeeding to enter the study.
- •A woman planning to become pregnant or planning to discontinue contraceptive precautions during approximately the first nine months of the study (Months 0-8).
- •Previous administration of components of the investigational vaccine.
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- •Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e. days 0-29) each dose of vaccine. Administration of some routine vaccines up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
- •Previous vaccination against human papillomavirus (HPV).
- •History of vaccination against Hepatitis A or a known clinical history of Hepatitis A disease.
- •History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.
- •Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination.
Outcomes
Primary Outcomes
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Time Frame: at Month 48
CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in subjects: 1. DNA- and sero-: HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0) 2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Secondary Outcomes
- Number of Subjects Reporting Serious Adverse Events (SAEs)(Throughout the entire study period (Month 0 to Month 48))
- Number of Subjects Reporting Medically Significant Conditions(Throughout entire study period (Month 0 to Month 48))
- Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types(at Month 48)
- Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen(at Month 48)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen(at Month 48)
- Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18(at Month 48)
- Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen(at Month 48)
- Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset(At Months 6, 7, 12, 24, 36 and 48)
- Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection(At Month 7)
- Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection(At Month 7)
- Number of Subjects Reporting Solicited Local and General Symptoms(Within 7 days after any vaccination)
- Number of Subjects Reporting Unsolicited Adverse Events(Within 30 days after any vaccination)
- Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)(Throughout the entire study (Month 0 to 48))
- Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus(Throughout the entire study period (Month 0 to Month 48))
- Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18(at Month 48)
- HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)(Month 0, 7, 12 and 24)
- HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)(Month 0, 7, 12, 24)
- Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus(At Months 6, 7, 12, 24, 36 & 48)
- Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection(At Month 7)
- Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)(At month 0, 7, 12, 24, 36 and 48)
- Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)(At Month 0, 7, 12, 24, 36 and 48)
- Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection(At Month 7)
- Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection(At Month 7)
- Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.(At Month 7)
- Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection(At Month 7)
- Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.(At Month 7)