Infections, PapillomavirusPhase 3NCT00122681
Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GlaxoSmithKline (GSK) Biologicals HPV-16/18
A Phase 3 study testing Cervarix™ and Havrix™-based investigational formulation in people with Infections, Papillomavirus, run by GlaxoSmithKline at 138 sites in 14 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 15 to 25 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infections, Papillomavirus
- What is being tested?
- Cervarix™ and Havrix™-based investigational formulation
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18,729 participants
- Where
- 138 sitesin 14 countries
- Study dates
- 6 May 2004to 26 Nov 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 25 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines.
- Hypersensitivity to latex.
- Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
- History of chronic condition(s) requiring treatment.
- Received immunoglobulins and/or blood product within 90 days preceding enrollment. Enrollment will be deferred until the subject is outside of specified window.
- Acute disease at the time of enrolment.
- Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed. Enrollment will be deferred until condition is resolved according to investigator's medical judgement.
Trial locations and contacts
138 sites in 14 countries.
138 sites in 14 countries
United States50 sites
GSK Investigational Site
Albuquerque, New Mexico, 87131
GSK Investigational Site
Arkansas City, Kansas, 67005
GSK Investigational Site
Augusta, Georgia, 30912
GSK Investigational Site
Austin, Texas, 78705
GSK Investigational Site
Bardstown, Kentucky, 40004
GSK Investigational Site
Birmingham, Alabama, 35233
GSK Investigational Site
Boulder, Colorado, 80303
GSK Investigational Site
Boulder, Colorado, 80304
GSK Investigational Site
Carnegie, Pennsylvania, 15106
GSK Investigational Site
Chapel Hill, North Carolina, 27514
GSK Investigational Site
Charlottesville, Virginia, 22903
GSK Investigational Site
Clearwater, Florida, 33759
GSK Investigational Site
Cleveland, Ohio, 44109
GSK Investigational Site
Coral Gables, Florida, 33134
GSK Investigational Site
Denver, Colorado, 80218
GSK Investigational Site
Erie, Pennsylvania, 16502
GSK Investigational Site
Erie, Pennsylvania, 16505
GSK Investigational Site
Erie, Pennsylvania, 16507
GSK Investigational Site
Erie, Pennsylvania, 16508
GSK Investigational Site
Fountain Valley, California, 92708
GSK Investigational Site
Honolulu, Hawaii, 96826
GSK Investigational Site
Houston, Texas, 77004
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Iowa City, Iowa, 52242
GSK Investigational Site
Lebanon, New Hampshire, 03756
GSK Investigational Site
Louisville, Colorado, 80027
GSK Investigational Site
Louisville, Kentucky, 40202
GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
Minneapolis, Minnesota, 55455
GSK Investigational Site
Morristown, New Jersey, 07960
GSK Investigational Site
New Bern, North Carolina, 28562
GSK Investigational Site
New York, New York, 10029
GSK Investigational Site
Omaha, Nebraska, 68131
GSK Investigational Site
Philadelphia, Pennsylvania, 19107
GSK Investigational Site
Philadelphia, Pennsylvania, 19114
GSK Investigational Site
Pittsburgh, Pennsylvania, 15236
GSK Investigational Site
Portland, Oregon, 97210
GSK Investigational Site
Poughkeepsie, New York, 12601
GSK Investigational Site
Salt Lake City, Utah, 84120
GSK Investigational Site
San Diego, California, 92108
GSK Investigational Site
San Francisco, California, 94115
GSK Investigational Site
Spokane, Washington, 99202
GSK Investigational Site
Spokane, Washington, 99218
GSK Investigational Site
Tulsa, Oklahoma, 74105
GSK Investigational Site
Vancouver, Washington, 98664
GSK Investigational Site
Webster, Texas, 77598
GSK Investigational Site
Wenatchee, Washington, 98801
GSK Investigational Site
West Palm Beach, Florida, 33409
GSK Investigational Site
Wichita, Kansas, 67205
GSK Investigational Site
Wichita, Kansas, 67207
Finland19 sites
GSK Investigational Site
Espoo, 02100
GSK Investigational Site
Helsinki, 00100
GSK Investigational Site
Helsinki, 00610
GSK Investigational Site
Jarvenpaa, 04400
GSK Investigational Site
Jyväskylä, 40100
GSK Investigational Site
Kerava, 04250
GSK Investigational Site
Kotka, 48100
GSK Investigational Site
Kouvola, 45100
GSK Investigational Site
Kuopio, 70100
GSK Investigational Site
Lahti, 15110
GSK Investigational Site
Lappeenranta, 53100
GSK Investigational Site
Mikkeli, 50100
GSK Investigational Site
Oulu, 90220
GSK Investigational Site
Pori, 28100
GSK Investigational Site
Rauma, 26100
GSK Investigational Site
Seinäjoki, 60100
GSK Investigational Site
Tampere, 33100
GSK Investigational Site
Turku, 20520
GSK Investigational Site
Vaasa, 65100
Germany19 sites
GSK Investigational Site
Berlin, 10119
GSK Investigational Site
Berlin, 13086
GSK Investigational Site
Dietzenbach, Hesse, 63128
GSK Investigational Site
Frankfurt am Main, Hesse, 60439
GSK Investigational Site
Frankfurt am Main, Hesse, 65936
GSK Investigational Site
Hamburg, 20246
GSK Investigational Site
Hamburg, 22143
GSK Investigational Site
Hamburg, 22149
GSK Investigational Site
Hamburg, 22159
GSK Investigational Site
Hanover, Lower Saxony, 30657
GSK Investigational Site
Karlsruhe, Baden-Wurttemberg, 76199
GSK Investigational Site
Leipzig, Saxony, 04109
GSK Investigational Site
Mainz, Rhineland-Palatinate, 55116
GSK Investigational Site
Munich, Bavaria, 80331
GSK Investigational Site
Munich, Bavaria, 80637
GSK Investigational Site
Nordhausen, Thuringia, 99734
GSK Investigational Site
Ravensburg, Baden-Wurttemberg, 88212
GSK Investigational Site
Rheinstetten, Baden-Wurttemberg, 76287
GSK Investigational Site
Würzburg, Bavaria, 97070
Canada11 sites
GSK Investigational Site
Beauport, Quebec, G1E 7G9
GSK Investigational Site
Edmonton, Alberta, T6G 2C8
GSK Investigational Site
Langley, British Columbia, V3A 4H9
GSK Investigational Site
Montreal, Quebec, H3T 1E2
GSK Investigational Site
Oshawa, Ontario, L1H 1C2
GSK Investigational Site
Ottawa, Ontario, K1S 1C2
GSK Investigational Site
St. John's, Newfoundland and Labrador, A1E 2C2
GSK Investigational Site
Toronto, Ontario, M4N 3M5
GSK Investigational Site
Truro, Nova Scotia, B2N 1L2
GSK Investigational Site
Waterloo, Ontario, N2J 1C4
GSK Investigational Site
Winnipeg, Manitoba, R3E 0J9
Australia6 sites
GSK Investigational Site
Adelaide, South Australia, 5000
GSK Investigational Site
Carlton, Melbourne, Victoria
GSK Investigational Site
Hobart, Tasmania
GSK Investigational Site
Melbourne, Victoria
GSK Investigational Site
Perth, Western Australia
GSK Investigational Site
Sydney, New South Wales, 4001
Philippines6 sites
GSK Investigational Site
Cavite
GSK Investigational Site
Laguna
GSK Investigational Site
Las Piñas
GSK Investigational Site
Los Banos, Laguna, 4027
GSK Investigational Site
Makati City, 1231
GSK Investigational Site
Manila, 1000
Spain6 sites
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Madrid, 28009
GSK Investigational Site
Marid, 28040
GSK Investigational Site
Móstoles, 28935
United Kingdom6 sites
GSK Investigational Site
Aberdeen, AB25 2ZN
GSK Investigational Site
London, SW17 0QT
GSK Investigational Site
London, W1P 1LB
GSK Investigational Site
Manchester, M13 9WL
GSK Investigational Site
Manchester, M15 6SX
GSK Investigational Site
Waterloo, Liverpool, L22 0LG
Belgium3 sites
GSK Investigational Site
Brussels, 1090
GSK Investigational Site
Edegem, 2650
GSK Investigational Site
Leuven, 3000
Brazil3 sites
GSK Investigational Site
Campinas, São Paulo
GSK Investigational Site
Curitiba, Paraná, 80069-900
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90035-903
Taiwan3 sites
GSK Investigational Site
Taipei, 100
GSK Investigational Site
Taipei, 112
GSK Investigational Site
Taipei, 114
Thailand3 sites
GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Bangkok, 10400
GSK Investigational Site
Bangkok, 10700
Italy2 sites
GSK Investigational Site
Milan, Lombardy, 20122
GSK Investigational Site
Modena, Emilia-Romagna, 41150
About this study
Official title: 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.
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.
Read the 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.
- Conditions
- Infections, Papillomavirus
- Being tested
- Cervarix™, Havrix™-based investigational formulation
- Medical subject headings
- Papillomavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cervarix™Biological
Also called GSK Biologicals HPV 16/18 VLP/AS04 vaccine
Intramuscular injection, 3 doses
Havrix™-based investigational formulationBiological
Intramuscular injection, 3 doses
| Study group | Role | What they receive |
|---|---|---|
| Cervarix Group | Experimental | Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6. Receives: Biological: Cervarix™ |
| Havrix Group | Active comparator | Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6. Receives: Biological: Havrix™-based investigational formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done in:
- DNA- and sero-: subjects 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).
- Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3
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)
CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done in subjects:
- 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)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Measured: at Month 48
Secondary outcomes (32)
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
CIN1+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects Reporting Solicited Local and General Symptoms
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include arthralgia, fatigue, fever (measured in degree celsius (°C) by axillary route), gastrointestinal symptoms, headache, myalgia, rash and urticaria.
Data are presented across the 3 doses.
Measured: Within 7 days after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events
Unsolicited adverse event (AE) covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Measured: Within 30 days after any vaccination
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Measured: Throughout the entire study period (Month 0 to Month 48)
Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Measured: Throughout the entire study (Month 0 to 48)
Number of Subjects Reporting Medically Significant Conditions
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Measured: Throughout entire study period (Month 0 to Month 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
Pregnancy outcomes are normal infant, premature infant, abnormal infant, elective termination, therapeutic abortion, ectopic pregnancy, spontaneous abortion, still birth, lost to follow-up, no pregnancy/molar pregnancy, pregnancy ongoing.
Measured: Throughout the entire study period (Month 0 to Month 48)
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Measured: at Month 48
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Oncogenic types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.
HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Oncogenic types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.
HRW-HPV = All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV = High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68
Measured: 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
CIN1+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Measured: at Month 48
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18
Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type (by PCR) over a 12-month interval (evaluations were planned at approximately 6-month intervals).
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18
Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type (by PCR) over a 12-month interval (evaluations were planned at approximately 6-month intervals).
Detection was done in subjects:
- DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
- Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Measured: 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
Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
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
Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.
Measured: 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
CIN2+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.
Oncogenic types detected included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline, regardless of initial serostatus.
Measured: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
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
CIN2+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.
Oncogenic types detected included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative at baseline, regardless of initial serostatus.
Measured: at Month 48
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
Cut-off values assessed for seropositivity include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Results are presented for the total group and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus by ELISA - seronegative (sero-) or seropositive (sero+)
Measured: At Months 6, 7, 12, 24, 36 & 48
Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset
Titers are given as Geometric Mean Titers (GMTs) expressed as ELISA Units per milliliter (EL.U/mL).
GMTs are presented for the total group and also stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus by ELISA [seronegative (sero-) or seropositive (sero+)].
Measured: At Months 6, 7, 12, 24, 36 and 48
HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)
HPV-16 V5 cut-off was defined as greater than or equal to 41 ELU/mL. Only seronegative subjects were analysed. Seronegative subjects are subjects who had an antibody titer of less than 41 ELU/mL before vaccination.
HPV-18 J4 cut-off was defined as greater than or equal to 110 EL.U/mL. Both seropositive and seronegative subjects were included in the analysis. Seropositive subjects were subjects with an antibody titer of greater than or equal to 110 EL.U/mL. Seronegative subjects were subjects with an antibody titer less than 110 EL.U/mL.
Measured: Month 0, 7, 12 and 24
HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)
Titers were expressed as GMTs in ELISA units per milliliter (EL.U/mL).
Measured: Month 0, 7, 12, 24
Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Seropositivity was defined as subjects with a titer equal to or greater than 40.
Subjects with an antibody titer smaller than 40 prior to vaccination were seronegative prior to vaccination and subjects with a titer equal to or greater than 40 were seropositive prior to vaccination.
Measured: At Month 0, 7, 12, 24, 36 and 48
Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Titers were expressed as GMTs.
Measured: At month 0, 7, 12, 24, 36 and 48
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection
GMT for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Measured: At Month 7
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.
Seroconversion rates for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence interval) was not calculated.
Measured: At Month 7
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection
GMTs for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Measured: At Month 7
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection
Seroconversion rates for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Measured: At Month 7
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection
GMTs for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Measured: At Month 7
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.
Seroconversion rates for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Measured: At Month 7
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection
GMTs for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Measured: At Month 7
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection
Seroconversion rates for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Measured: At Month 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2005 (estimated)
- Study start6 May 2004
- Primary completion3 Nov 2006
- Study completion26 Nov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Infections, PapillomavirusStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18,729 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00122681
- Sponsor's protocol ID
- 580299/008
- Status last verified
- Aug 2017
- First submitted
- 20 Jul 2005
- Last updated
- 20 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.
PubMed 41276263Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Bly A, Gray P, Harjula K, Heikkila K, Hokkanen M, Karttunen H, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petaja T, Pukkala E, Soderlund-Strand A, Veivo U, Dillner J. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial. BMJ Open. 2021 Dec 30;11(12):e050669. doi: 10.1136/bmjopen-2021-050669.
PubMed 35149535Welby S, Rosillon D, Feng Y, Borys D. Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18-25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016. Expert Rev Vaccines. 2022 Mar;21(3):407-413. doi: 10.1080/14760584.2022.2021077. Epub 2022 Jan 24.
PubMed 34939897Adhikari I, Eriksson T, Luostarinen T, Apter D, Lehtinen M. Is the risk of cervical atypia associated with the interval between menarche and the start of sexual activity? A population-based cohort study. BMJ Open. 2019 Sep 11;9(9):e030091. doi: 10.1136/bmjopen-2019-030091.
PubMed 31511286Castellsague X, Paavonen J, Jaisamrarn U, Wheeler CM, Skinner SR, Lehtinen M, Naud P, Chow SN, Del Rosario-Raymundo MR, Teixeira JC, Palmroth J, de Carvalho NS, Germar MJ, Peters K, Garland SM, Szarewski A, Poppe WA, Romanowski B, Schwarz TF, Tjalma WA, Bosch FX, Bozonnat MC, Struyf F, Dubin G, Rosillon D, Baril L; HPV PATRICIA Study Group. Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial. BMC Infect Dis. 2014 Oct 30;14:551. doi: 10.1186/s12879-014-0551-y.
PubMed 25927224Apter D, Wheeler CM, Paavonen J, Castellsague X, Garland SM, Skinner SR, Naud P, Salmeron J, Chow SN, Kitchener HC, Teixeira JC, Jaisamrarn U, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Mindel A, de Sutter P, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Efficacy of human papillomavirus 16 and 18 (HPV-16/18) AS04-adjuvanted vaccine against cervical infection and precancer in young women: final event-driven analysis of the randomized, double-blind PATRICIA trial. Clin Vaccine Immunol. 2015 Apr;22(4):361-73. doi: 10.1128/CVI.00591-14. Epub 2015 Feb 4.
PubMed 25651922Struyf F, Colau B, Wheeler CM, Naud P, Garland S, Quint W, Chow SN, Salmeron J, Lehtinen M, Del Rosario-Raymundo MR, Paavonen J, Teixeira JC, Germar MJ, Peters K, Skinner SR, Limson G, Castellsague X, Poppe WA, Ramjattan B, Klein TD, Schwarz TF, Chatterjee A, Tjalma WA, Diaz-Mitoma F, Lewis DJ, Harper DM, Molijn A, van Doorn LJ, David MP, Dubin G; HPV PATRICIA Study Group. Post hoc analysis of the PATRICIA randomized trial of the efficacy of human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against incident and persistent infection with nonvaccine oncogenic HPV types using an alternative multiplex type-specific PCR assay for HPV DNA. Clin Vaccine Immunol. 2015 Feb;22(2):235-44. doi: 10.1128/CVI.00457-14. Epub 2014 Dec 24.
PubMed 25540273Castellsague X, Naud P, Chow SN, Wheeler CM, Germar MJ, Lehtinen M, Paavonen J, Jaisamrarn U, Garland SM, Salmeron J, Apter D, Kitchener H, Teixeira JC, Skinner SR, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, de Carvalho NS, Peters K, Tjalma WA, Safaeian M, Raillard A, Descamps D, Struyf F, Dubin G, Rosillon D, Baril L. Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA. J Infect Dis. 2014 Aug 15;210(4):517-34. doi: 10.1093/infdis/jiu139. Epub 2014 Mar 8.
PubMed 24610876Jaisamrarn U, Castellsague X, Garland SM, Naud P, Palmroth J, Del Rosario-Raymundo MR, Wheeler CM, Salmeron J, Chow SN, Apter D, Teixeira JC, Skinner SR, Hedrick J, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, de Carvalho NS, Germar MJ, Peters K, Paavonen J, Bozonnat MC, Descamps D, Struyf F, Dubin GO, Rosillon D, Baril L; HPV PATRICIA Study Group. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study. PLoS One. 2013 Nov 19;8(11):e79260. doi: 10.1371/journal.pone.0079260. eCollection 2013.
PubMed 24260180Valve P, Lehtinen-Jacks S, Eriksson T, Lehtinen M, Lindfors P, Saha MT, Rimpela A, Angle S. LINDA - a solution-focused low-intensity intervention aimed at improving health behaviors of young females: a cluster-randomized controlled trial. BMC Public Health. 2013 Nov 4;13:1044. doi: 10.1186/1471-2458-13-1044.
PubMed 24188719Howell-Jones R, Soldan K, Wetten S, Mesher D, Williams T, Gill ON, Hughes G. Declining genital Warts in young women in england associated with HPV 16/18 vaccination: an ecological study. J Infect Dis. 2013 Nov 1;208(9):1397-403. doi: 10.1093/infdis/jit361.
PubMed 24092908Szarewski A, Skinner SR, Garland SM, Romanowski B, Schwarz TF, Apter D, Chow SN, Paavonen J, Del Rosario-Raymundo MR, Teixeira JC, De Carvalho NS, Castro-Sanchez M, Castellsague X, Poppe WA, De Sutter P, Huh W, Chatterjee A, Tjalma WA, Ackerman RT, Martens M, Papp KA, Bajo-Arenas J, Harper DM, Torne A, David MP, Struyf F, Lehtinen M, Dubin G. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation. J Infect Dis. 2013 Nov 1;208(9):1391-6. doi: 10.1093/infdis/jit360.
PubMed 24092907Roset Bahmanyar E, Paavonen J, Naud P, Salmeron J, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Jaisamrarn U, Limson GA, Garland SM, Szarewski A, Romanowski B, Aoki F, Schwarz TF, Poppe WA, De Carvalho NS, Harper DM, Bosch FX, Raillard A, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Prevalence and risk factors for cervical HPV infection and abnormalities in young adult women at enrolment in the multinational PATRICIA trial. Gynecol Oncol. 2012 Dec;127(3):440-50. doi: 10.1016/j.ygyno.2012.08.033. Epub 2012 Aug 30.
PubMed 22940493Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsague X, Skinner SR, Apter D, Naud P, Salmeron J, Chow SN, Kitchener H, Teixeira JC, Hedrick J, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, De Carvalho NS, Germar MJ, Peters K, Mindel A, De Sutter P, Bosch FX, David MP, Descamps D, Struyf F, Dubin G; HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan;13(1):89-99. doi: 10.1016/S1470-2045(11)70286-8. Epub 2011 Nov 8.
PubMed 22075171Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, Naud P, Salmeron J, Chow SN, Apter D, Kitchener H, Teixeira JC, Skinner SR, Jaisamrarn U, Limson G, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Harper DM, Huh W, Hardt K, Zahaf T, Descamps D, Struyf F, Dubin G, Lehtinen M; HPV PATRICIA Study Group. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan;13(1):100-10. doi: 10.1016/S1470-2045(11)70287-X. Epub 2011 Nov 8.
PubMed 22075170
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT00122681
- Acronym / sponsor ID
- 580299/008
- Conditions
- Infections, Papillomavirus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18,729 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 6 May 2004 (actual)
- Primary completion
- 3 Nov 2006 (actual)
- Study completion
- 26 Nov 2009 (actual)
- First posted
- 22 Jul 2005 (estimated)
- Results
- Posted 20 Jan 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cervarix Group | Experimental | Biological: Cervarix™Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6. |
| Havrix Group | Active comparator | Biological: Havrix™-based investigational formulationSubjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6. |
Who may qualify
- Ages
- 15 to 25 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cervarix™Also: GSK Biologicals HPV 16/18 VLP/AS04 vaccineIntramuscular injection, 3 doses | Biological | Cervarix Group |
| Havrix™-based investigational formulationIntramuscular injection, 3 doses | Biological | Havrix Group |
Primary outcome
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: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3
CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: 1. DNA- and sero-: subjects 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 DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
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.
32 secondary outcomes
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
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects Reporting Solicited Local and General Symptoms
Time frame: Within 7 days after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events
Time frame: Within 30 days after any vaccination
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: Throughout the entire study period (Month 0 to Month 48)
Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)
Time frame: Throughout the entire study (Month 0 to 48)
Number of Subjects Reporting Medically Significant Conditions
Time frame: Throughout entire study period (Month 0 to Month 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
Time frame: Throughout the entire study period (Month 0 to Month 48)
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Time frame: at Month 48
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Time frame: 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
Time frame: at Month 48
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18
Time frame: 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
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
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
Time frame: 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
Time frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3
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
Time frame: at Month 48
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
Time frame: At Months 6, 7, 12, 24, 36 & 48
Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset
Time frame: At Months 6, 7, 12, 24, 36 and 48
HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)
Time frame: Month 0, 7, 12 and 24
HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)
Time frame: Month 0, 7, 12, 24
Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Time frame: At Month 0, 7, 12, 24, 36 and 48
Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Time frame: At month 0, 7, 12, 24, 36 and 48
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection
Time frame: At Month 7
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.
Time frame: At Month 7
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection
Time frame: At Month 7
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection
Time frame: At Month 7
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection
Time frame: At Month 7
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.
Time frame: At Month 7
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection
Time frame: At Month 7
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection
Time frame: At Month 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41276263Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.
- Derived from this study: PubMed 35149535Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Bly A, Gray P, Harjula K, Heikkila K, Hokkanen M, Karttunen H, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petaja T, Pukkala E, Soderlund-Strand A, Veivo U, Dillner J. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial. BMJ Open. 2021 Dec 30;11(12):e050669. doi: 10.1136/bmjopen-2021-050669.
- Derived from this study: PubMed 34939897Welby S, Rosillon D, Feng Y, Borys D. Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18-25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016. Expert Rev Vaccines. 2022 Mar;21(3):407-413. doi: 10.1080/14760584.2022.2021077. Epub 2022 Jan 24.
- Derived from this study: PubMed 31511286Adhikari I, Eriksson T, Luostarinen T, Apter D, Lehtinen M. Is the risk of cervical atypia associated with the interval between menarche and the start of sexual activity? A population-based cohort study. BMJ Open. 2019 Sep 11;9(9):e030091. doi: 10.1136/bmjopen-2019-030091.
- Derived from this study: PubMed 25927224Castellsague X, Paavonen J, Jaisamrarn U, Wheeler CM, Skinner SR, Lehtinen M, Naud P, Chow SN, Del Rosario-Raymundo MR, Teixeira JC, Palmroth J, de Carvalho NS, Germar MJ, Peters K, Garland SM, Szarewski A, Poppe WA, Romanowski B, Schwarz TF, Tjalma WA, Bosch FX, Bozonnat MC, Struyf F, Dubin G, Rosillon D, Baril L; HPV PATRICIA Study Group. Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial. BMC Infect Dis. 2014 Oct 30;14:551. doi: 10.1186/s12879-014-0551-y.
- Derived from this study: PubMed 25651922Apter D, Wheeler CM, Paavonen J, Castellsague X, Garland SM, Skinner SR, Naud P, Salmeron J, Chow SN, Kitchener HC, Teixeira JC, Jaisamrarn U, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Mindel A, de Sutter P, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Efficacy of human papillomavirus 16 and 18 (HPV-16/18) AS04-adjuvanted vaccine against cervical infection and precancer in young women: final event-driven analysis of the randomized, double-blind PATRICIA trial. Clin Vaccine Immunol. 2015 Apr;22(4):361-73. doi: 10.1128/CVI.00591-14. Epub 2015 Feb 4.
- Derived from this study: PubMed 25540273Struyf F, Colau B, Wheeler CM, Naud P, Garland S, Quint W, Chow SN, Salmeron J, Lehtinen M, Del Rosario-Raymundo MR, Paavonen J, Teixeira JC, Germar MJ, Peters K, Skinner SR, Limson G, Castellsague X, Poppe WA, Ramjattan B, Klein TD, Schwarz TF, Chatterjee A, Tjalma WA, Diaz-Mitoma F, Lewis DJ, Harper DM, Molijn A, van Doorn LJ, David MP, Dubin G; HPV PATRICIA Study Group. Post hoc analysis of the PATRICIA randomized trial of the efficacy of human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against incident and persistent infection with nonvaccine oncogenic HPV types using an alternative multiplex type-specific PCR assay for HPV DNA. Clin Vaccine Immunol. 2015 Feb;22(2):235-44. doi: 10.1128/CVI.00457-14. Epub 2014 Dec 24.
- Derived from this study: PubMed 24610876Castellsague X, Naud P, Chow SN, Wheeler CM, Germar MJ, Lehtinen M, Paavonen J, Jaisamrarn U, Garland SM, Salmeron J, Apter D, Kitchener H, Teixeira JC, Skinner SR, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, de Carvalho NS, Peters K, Tjalma WA, Safaeian M, Raillard A, Descamps D, Struyf F, Dubin G, Rosillon D, Baril L. Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA. J Infect Dis. 2014 Aug 15;210(4):517-34. doi: 10.1093/infdis/jiu139. Epub 2014 Mar 8.
- Derived from this study: PubMed 24260180Jaisamrarn U, Castellsague X, Garland SM, Naud P, Palmroth J, Del Rosario-Raymundo MR, Wheeler CM, Salmeron J, Chow SN, Apter D, Teixeira JC, Skinner SR, Hedrick J, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, de Carvalho NS, Germar MJ, Peters K, Paavonen J, Bozonnat MC, Descamps D, Struyf F, Dubin GO, Rosillon D, Baril L; HPV PATRICIA Study Group. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study. PLoS One. 2013 Nov 19;8(11):e79260. doi: 10.1371/journal.pone.0079260. eCollection 2013.
- Derived from this study: PubMed 24188719Valve P, Lehtinen-Jacks S, Eriksson T, Lehtinen M, Lindfors P, Saha MT, Rimpela A, Angle S. LINDA - a solution-focused low-intensity intervention aimed at improving health behaviors of young females: a cluster-randomized controlled trial. BMC Public Health. 2013 Nov 4;13:1044. doi: 10.1186/1471-2458-13-1044.
- Derived from this study: PubMed 24092908Howell-Jones R, Soldan K, Wetten S, Mesher D, Williams T, Gill ON, Hughes G. Declining genital Warts in young women in england associated with HPV 16/18 vaccination: an ecological study. J Infect Dis. 2013 Nov 1;208(9):1397-403. doi: 10.1093/infdis/jit361.
- Derived from this study: PubMed 24092907Szarewski A, Skinner SR, Garland SM, Romanowski B, Schwarz TF, Apter D, Chow SN, Paavonen J, Del Rosario-Raymundo MR, Teixeira JC, De Carvalho NS, Castro-Sanchez M, Castellsague X, Poppe WA, De Sutter P, Huh W, Chatterjee A, Tjalma WA, Ackerman RT, Martens M, Papp KA, Bajo-Arenas J, Harper DM, Torne A, David MP, Struyf F, Lehtinen M, Dubin G. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation. J Infect Dis. 2013 Nov 1;208(9):1391-6. doi: 10.1093/infdis/jit360.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
138 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cervarix™ and Havrix™-based investigational formulation in people with Infections, Papillomavirus, run by GlaxoSmithKline at 138 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 138 sites in United States, Finland, Germany, Canada, Australia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00122681, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018.