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

NCT ID: NCT00294047

Last Updated: 2020-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 5752 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-16
• Study Completion Date: 2014-01-29

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.

Detailed Description

The Protocol Posting has been updated due to protocol amendment 5 and in order to comply with the FDA Amendment Act, Sep 2007.

Conditions

Infections, Papillomavirus; Papillomavirus Vaccines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Cervarix Group

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.

Group Type: EXPERIMENTAL

Cervarix

Intervention Type: BIOLOGICAL

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

Aluminium Hydroxide Group

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.

Group Type: PLACEBO_COMPARATOR

Placebo control

Intervention Type: BIOLOGICAL

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

Interventions

Cervarix

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

Intervention Type: BIOLOGICAL

Placebo control

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed (and no cervical sample can be taken). Enrolment will be deferred until condition is resolved according to investigators medical judgement.

• Minimum Eligible Age: 26 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Golden, Colorado, United States

GSK Investigational Site

Coral Gables, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Augusta, Georgia, United States

GSK Investigational Site

Iowa City, Iowa, United States

GSK Investigational Site

Wichita, Kansas, United States

GSK Investigational Site

Bardstown, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Chaska, Minnesota, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Lebanon, New Hampshire, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Syracuse, New York, United States

GSK Investigational Site

Chapel Hill, North Carolina, United States

GSK Investigational Site

New Bern, North Carolina, United States

GSK Investigational Site

Akron, Ohio, United States

GSK Investigational Site

Cleveland, Ohio, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Carnegie, Pennsylvania, United States

GSK Investigational Site

Erie, Pennsylvania, United States

GSK Investigational Site

Erie, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Wexford, Pennsylvania, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

South Jordan, Utah, United States

GSK Investigational Site

Wenatchee, Washington, United States

GSK Investigational Site

La Crosse, Wisconsin, United States

GSK Investigational Site

Parkville, Victoria, Australia

GSK Investigational Site

Perth, Western Australia, Australia

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Truro, Nova Scotia, Canada

GSK Investigational Site

Waterloo, Ontario, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Sherbrooke, Quebec, Canada

GSK Investigational Site

Cuenavaca, Morelos, Mexico

GSK Investigational Site

Jojutla / Morelos, , Mexico

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Delft, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Lima, , Peru

GSK Investigational Site

Laguna, , Philippines

GSK Investigational Site

San Pablo, , Philippines

GSK Investigational Site

Taft Avenue, Manila, , Philippines

GSK Investigational Site

Almada, , Portugal

GSK Investigational Site

Coimbra, , Portugal

GSK Investigational Site

Lisbon, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Setúbal, , Portugal

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Northwood, Middlesex, United Kingdom

GSK Investigational Site

Aberdeen, , United Kingdom

GSK Investigational Site

Cardiff, , United Kingdom

GSK Investigational Site

Gateshead, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

Countries

United States; Australia; Canada; Mexico; Netherlands; Peru; Philippines; Portugal; Russia; Singapore; Thailand; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 19221517 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25189358 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18845199 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27373900 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27998562 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31824976 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31273942 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26685704 (View on PubMed)

Study Documents

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

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Other Identifiers

2005-002546-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

104820

Identifier Type: -

Identifier Source: org_study_id