Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older

NCT00294047 | Completed Phase 3 Results

• 2 other identifiers: 1048202005-002546-20
• Study Type: interventional
• Target: 5,752
• Locations: 12 countries
• Sites: 75

Brief Summary

This is a multicentre study in which women were planned to receive either the Human Papillomavirus Vaccine (HPV) vaccine or control. Under Protocol Amendment 3, study participation will last approximately 48 months and involves a total of eleven scheduled visits. Under Protocol Amendment 4, study participation will last up to 84 months and involves a maximum of seventeen scheduled visits.

Conditions

Infections, Papillomavirus; Papillomavirus Vaccines

Keywords

Vaccine; Human papillomavirus; Cervical Cancer; Cervical Infection

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.

  CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) * Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

  Up to Month 48

• Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).

  CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by 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.

  Up to Month 48

• Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.

  CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

  Up to Month 84

• Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).

  CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by 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.

  Up to Month 84

Secondary Outcomes (45)

• Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18

  Up to Month 48

• Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18

  Up to Month 48

• Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.

  Up to Month 48

• Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.

  Up to Month 48

• Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen

  Up to Month 48

Study Arms (2)

Cervarix Group

EXPERIMENTAL

Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

Biological: Cervarix

Aluminium Hydroxide Group

PLACEBO COMPARATOR

Subjects received 3 doses of Aluminium Hydroxide \[Al(OH)3\]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

Biological: Placebo control

Interventions

Cervarix BIOLOGICAL

Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Cervarix Group

Placebo control BIOLOGICAL

Subjects were planned to receive three doses of the control vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Aluminium Hydroxide Group

Eligibility Criteria

• Age: 26 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A woman who the investigator believes that she can and will comply with the requirements of the protocol.
• A women of at least 26 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to enrolment.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Subject must have intact cervix.
• Subject must have a negative urine pregnancy test. This test is not applicable to women of non-childbearing potential.
• Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using an effective method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.

You may not qualify if:

• Pregnant or breastfeeding (women must be at least three months post-pregnancy and not breastfeeding to enter the study).
• A women planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose (Month 0 - 8).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 84).
• 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) the first dose of study vaccine. Planned administration/administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
• Previous administration of components of the investigational vaccine
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
• History of HPV infection/treatment or planned treatment to evaluate an abnormal cervical cytology (Pap smear) test, e.g. colposcopy.
• 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 vaccine.
• Hypersensitivity to latex.
• Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
• History of chronic condition(s) requiring treatment.
• Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine, or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
• Acute disease at the time of enrolment.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (75)

GSK Investigational Site

Fountain Valley, California, 92708, United States

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GSK Investigational Site

Aurora, Colorado, 80045, United States

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Golden, Colorado, 80401, United States

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Coral Gables, Florida, 33134, United States

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Miami, Florida, 33136, United States

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Augusta, Georgia, 30912, United States

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Iowa City, Iowa, 52242, United States

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Wichita, Kansas, 67207, United States

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Bardstown, Kentucky, 40004, United States

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Louisville, Kentucky, 40202, United States

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Chaska, Minnesota, 55318, United States

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Omaha, Nebraska, 68131, United States

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Lebanon, New Hampshire, 03756, United States

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Albuquerque, New Mexico, 87131, United States

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Syracuse, New York, 13057, United States

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Chapel Hill, North Carolina, 27514, United States

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New Bern, North Carolina, 28562, United States

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Akron, Ohio, 44311, United States

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Cleveland, Ohio, 44122, United States

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Tulsa, Oklahoma, 74105, United States

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Portland, Oregon, 97210, United States

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Carnegie, Pennsylvania, 15106, United States

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Erie, Pennsylvania, 16507, United States

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Erie, Pennsylvania, 16508, United States

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Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Pittsburgh, Pennsylvania, 15236, United States

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Wexford, Pennsylvania, 15090, United States

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Austin, Texas, 78705, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77030, United States

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Salt Lake City, Utah, 84109, United States

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Salt Lake City, Utah, 84121, United States

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South Jordan, Utah, 84095, United States

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Wenatchee, Washington, 98801, United States

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La Crosse, Wisconsin, 54601, United States

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Parkville, Victoria, 3052, Australia

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Perth, Western Australia, Australia

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Edmonton, Alberta, T6G 2C8, Canada

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Vancouver, British Columbia, V6H 3N1, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Truro, Nova Scotia, B2N 1L2, Canada

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Waterloo, Ontario, N2L 6H6, Canada

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Québec, Quebec, G1S 2L6, Canada

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Sherbrooke, Quebec, J1H 1Z1, Canada

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Cuenavaca, Morelos, 62430, Mexico

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Jojutla / Morelos, Mexico

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Amsterdam, 1007 MB, Netherlands

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Delft, 2625 AD, Netherlands

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GSK Investigational Site

Rotterdam, 3015 CE, Netherlands

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GSK Investigational Site

Lima, Peru

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Laguna, Philippines

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San Pablo, Philippines

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GSK Investigational Site

Taft Avenue, Manila, 1700, Philippines

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Almada, 2805-267 Almada, Portugal

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Coimbra, 3000-075 Coimbra, Portugal

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Lisbon, 1200-831 Lisboa, Portugal

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Porto, 4200-023 Porto, Portugal

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Setúbal, 2910-446 Setúbal, Portugal

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Moscow, 109263, Russia

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Moscow, 115 478, Russia

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Moscow, 117997, Russia

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Saint Petersburg, 190020, Russia

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Saint Petersburg, 199034, Russia

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Yekaterinburg, 620073, Russia

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Singapore, 119074, Singapore

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Singapore, 229899, Singapore

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Bangkok, 10400, Thailand

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GSK Investigational Site

Bangkok, 10700, Thailand

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Northwood, Middlesex, HA6 2RN, United Kingdom

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Aberdeen, AB25 7ZD, United Kingdom

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Cardiff, CF14 4XN, United Kingdom

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GSK Investigational Site

Gateshead, NE9 6SX, United Kingdom

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GSK Investigational Site

London, EC1M 6BQ, United Kingdom

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GSK Investigational Site

Manchester, M13 9WL, United Kingdom

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Related Publications (9)

• Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.

  PMID: 19221517 BACKGROUND

• Skinner SR, Szarewski A, Romanowski B, Garland SM, Lazcano-Ponce E, Salmeron J, Del Rosario-Raymundo MR, Verheijen RH, Quek SC, da Silva DP, Kitchener H, Fong KL, Bouchard C, Money DM, Ilancheran A, Cruickshank ME, Levin MJ, Chatterjee A, Stapleton JT, Martens M, Quint W, David MP, Meric D, Hardt K, Descamps D, Geeraerts B, Struyf F, Dubin G; VIVIANE Study Group. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet. 2014 Dec 20;384(9961):2213-27. doi: 10.1016/S0140-6736(14)60920-X. Epub 2014 Sep 1.

  PMID: 25189358 BACKGROUND

• Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.

  PMID: 18845199 BACKGROUND

• Wheeler CM, Skinner SR, Del Rosario-Raymundo MR, Garland SM, Chatterjee A, Lazcano-Ponce E, Salmeron J, McNeil S, Stapleton JT, Bouchard C, Martens MG, Money DM, Quek SC, Romanowski B, Vallejos CS, Ter Harmsel B, Prilepskaya V, Fong KL, Kitchener H, Minkina G, Lim YKT, Stoney T, Chakhtoura N, Cruickshank ME, Savicheva A, da Silva DP, Ferguson M, Molijn AC, Quint WGV, Hardt K, Descamps D, Suryakiran PV, Karkada N, Geeraerts B, Dubin G, Struyf F; VIVIANE Study Group. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet Infect Dis. 2016 Oct;16(10):1154-1168. doi: 10.1016/S1473-3099(16)30120-7. Epub 2016 Jun 28.

  PMID: 27373900 BACKGROUND

• Wheeler CM, Struyf F; HPV-015 study group. The safety of Cervarix? - Authors' reply. Lancet Infect Dis. 2017 Jan;17(1):20-21. doi: 10.1016/S1473-3099(16)30540-0. No abstract available.

  PMID: 27998562 BACKGROUND

• 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.

  PMID: 41276263 DERIVED

• Chen J, Gopala K, Akarsh PK, Struyf F, Rosillon D. Prevalence and Incidence of Human Papillomavirus (HPV) Infection Before and After Pregnancy: Pooled Analysis of the Control Arms of Efficacy Trials of HPV-16/18 AS04-Adjuvanted Vaccine. Open Forum Infect Dis. 2019 Dec 4;6(12):ofz486. doi: 10.1093/ofid/ofz486. eCollection 2019 Dec.

  PMID: 31824976 DERIVED

• Rosillon D, Baril L, Del Rosario-Raymundo MR, Wheeler CM, Skinner SR, Garland SM, Salmeron J, Lazcano-Ponce E, Vallejos CS, Stoney T, Ter Harmsel B, Lim TYK, Quek SC, Minkina G, McNeil SA, Bouchard C, Fong KL, Money D, Ilancheran A, Savicheva A, Cruickshank M, Chatterjee A, Fiander A, Martens M, Bozonnat MC, Struyf F, Dubin G, Castellsague X. Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies. Cancer Med. 2019 Aug;8(10):4938-4953. doi: 10.1002/cam4.1879. Epub 2019 Jul 5.

  PMID: 31273942 DERIVED

• Skinner SR, Wheeler CM, Romanowski B, Castellsague X, Lazcano-Ponce E, Del Rosario-Raymundo MR, Vallejos C, Minkina G, Pereira Da Silva D, McNeil S, Prilepskaya V, Gogotadze I, Money D, Garland SM, Romanenko V, Harper DM, Levin MJ, Chatterjee A, Geeraerts B, Struyf F, Dubin G, Bozonnat MC, Rosillon D, Baril L; VIVIANE Study Group. Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study. Int J Cancer. 2016 May 15;138(10):2428-38. doi: 10.1002/ijc.29971.

  PMID: 26685704 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Papillomavirus Infections; Uterine Cervical Neoplasms

Interventions

human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2006
• First Posted: February 20, 2006
• Study Start: February 16, 2006
• Primary Completion: January 29, 2014
• Study Completion: January 29, 2014
• Last Updated: January 2, 2020
• Results First Posted: March 27, 2012

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (36); PE (1); NL (3); PH (3); PT (5); TH (2); GB (6); SG (2); CA (7); ME (2); RU (6); AU (2)