Immunogenicity of GlaxoSmithKline Biological's Human Papillomavirus (HPV) Vaccine (580299) Versus Merck's Gardasil® in Healthy Females 18-45 Years of Age

NCT00423046 | Completed Phase 3 Results

• 1 other identifier: 108933
• Study Type: interventional
• Target: 1,106
• Locations: 1 country
• Sites: 40

Brief Summary

HPV infection has been established as a necessary cause of cervical cancer. GSK Biologicals has developed an HPV-16/18 L1 VLP AS04 vaccine (Cervarix TM) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in \> 70%, approximately, of all cervical cancers. Recently, Merck's HPV vaccine Gardasil® \[quadrivalent human papillomavirus (HPV-6,11,16,18 L1 VLP) recombinant vaccine\] has been approved by the FDA for prevention of genital tract cancers and pre-cancers and genital warts in females. Although the GSK HPV vaccine and Gardasil® have different compositions and are expected to have different efficacy profiles, each vaccine targets prevention of HPV-16 and 18 genital tract cancers and pre-cancers. Therefore, a comparison of the immunogenicity of the two vaccines is warranted. This Phase 3b study is designed to compare the immunogenicity of the GSK vaccine (HPV-16/18) to Gardasil® in healthy adult females 18-45 years of age. The Protocol Posting has been updated as the study will be extended by 3 additional years.

Conditions

Infections, Papillomavirus; Papillomavirus Vaccines

Keywords

Vaccines; Cervical cancer; Immunogenicity; Humans; Safety; Viral infections; Human papillomavirus (HPV); Comparative study; Human papillomavirus vaccine; Adults

Outcome Measures

Primary Outcomes (1)

• Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Neutralizing Antibodies

  Titers are displayed as Geometric Mean Titers (GMTs). The titer is the serum dilution giving a 50 percent reduction of the signal compared to a control without serum.

  At Month 7

Secondary Outcomes (30)

• Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Neutralizing Antibodies

  At Month 6, 7, 12, 18, 24, 36, 48 and 60

• Number of Subjects With Antibody Titers (Neutralizing Assay) Against Other Oncongenic HPV Types Greater Than or Equal to the Cut-off Value

  At Month 7

• Titers of Antibodies to Other Oncogenic HPV Types Measured by Neutralization Assay

  At Month 7

• Number of Subjects With Antibody Titers (Neutralizing Assay) Against Human Papilloma Virus 16 (Anti-HPV-16) and Human Papilloma Virus 18 (Anti-HPV-18) Greater Than or Equal to the Cut-off Value

  At Month 6, 7, 12, 18, 24, 36, 48 and 60

• Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Immunoglobulin G (IgG) Antibody Titers Above Cut-off Values, Measured by Enzyme-linked Immunosorbent Assay (ELISA)

  At Month 6, 7, 12, 18, 24, 36, 48 and 60

Study Arms (2)

Cervarix Group

EXPERIMENTAL

Subjects received 3 doses of GSK Biologicals human papillomavirus \[HPV\]16/18 vaccine 580299 (CervarixTM) at Months 0, 1 and 6 and a dose of placebo at Month 2. All doses were administered by intramuscular injection in the deltoid muscle of the upper arm.

Biological: GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM); Biological: Placebo

Gardasil Group

ACTIVE COMPARATOR

Subjects received 3 doses of Gardasil® (Merck's human papillomavirus \[HPV\] vaccine) at Months 0, 2 and 6 and a dose of placebo at Month 1. All doses were administered by intramuscular injection in the deltoid muscle of the upper arm.

Biological: Gardasil ® (Merck & Co. Inc); Biological: Placebo

Interventions

GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM) BIOLOGICAL

Three doses administered intramuscularly at months 0, 1 and 6

Also known as: Cervarix

Cervarix Group

Gardasil ® (Merck & Co. Inc) BIOLOGICAL

Three doses administered intramuscularly at months 0, 2 and 6

Gardasil Group

Placebo BIOLOGICAL

One dose administered intramuscularly at month 1 to maintain blinding

Gardasil Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A woman whom the investigator believes that she or her legally acceptable representative (in the event that the subject is illiterate) 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 18 and 45 years of age at the time of the first vaccination.
• Written informed consent must be obtained from the subject prior to enrollment.
• Subject must be free of obvious health problems as established by medical history and history-directed clinical examination before entering into the study.
• Subject must have a negative urine pregnancy test.
• Subject must be of non-childbearing potential, or if she is of child bearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
• Subject must have an intact cervix.

You may not qualify if:

• 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 up to Month 60.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study period up to Month 60.
• 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 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.
• 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 eight months of the study (Months 0-8).
• Previous administration of components of the investigational vaccine
• Previous or planned vaccination against HPV outside of this protocol.
• 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 significant medical conditions and currently under treatment.
• Received immunoglobulins and/or blood product within 90 days preceding enrolment or planned administration during the study period up to Month 60. Enrollment will be deferred until the subject is outside of specified window.
• Acute disease at the time of enrolment. Enrollment will be deferred until condition is resolved. All vaccines can be administered to persons with a minor illness
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (40)

GSK Investigational Site

Chandler, Arizona, 85224, United States

Location

GSK Investigational Site

San Diego, California, 92123, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Vista, California, 92083, United States

Location

GSK Investigational Site

West Covina, California, 91790, United States

Location

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Louisville, Colorado, 80027, United States

Location

GSK Investigational Site

Boynton Beach, Florida, 33437, United States

Location

GSK Investigational Site

Coral Gables, Florida, 33134, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30342, United States

Location

GSK Investigational Site

Boise, Idaho, 83642, United States

Location

GSK Investigational Site

Arkansas City, Kansas, 67005, United States

Location

GSK Investigational Site

Wichita, Kansas, 67207, United States

Location

GSK Investigational Site

Bardstown, Kentucky, 40004, United States

Location

GSK Investigational Site

Milford, Massachusetts, 01757, United States

Location

GSK Investigational Site

Stevensville, Michigan, 49127, United States

Location

GSK Investigational Site

Chaska, Minnesota, 55318, United States

Location

GSK Investigational Site

Saint Paul, Minnesota, 55108, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68131, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

Location

GSK Investigational Site

The Bronx, New York, 10461, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45249, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44122, United States

Location

GSK Investigational Site

Willoughby Hills, Ohio, 44094, United States

Location

GSK Investigational Site

Carnegie, Pennsylvania, 15106, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16507, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16508, United States

Location

GSK Investigational Site

Lancaster, Pennsylvania, 17601, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Upper Saint Clair, Pennsylvania, 15241, United States

Location

GSK Investigational Site

Warwick, Rhode Island, 02886, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84109, United States

Location

GSK Investigational Site

Tacoma, Washington, 98418, United States

Location

GSK Investigational Site

Walla Walla, Washington, 99362, United States

Location

GSK Investigational Site

Wenatchee, Washington, 98801, United States

Location

Related Publications (10)

• Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology. 121:S1-S9.

  BACKGROUND

• Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, Zepp F, Carletti I, Dessy FJ, Trofa AF, Schuind A, Dubin G; HPV-010 Study Group. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years. Hum Vaccin. 2009 Oct;5(10):705-19. doi: 10.4161/hv.5.10.9518. Epub 2009 Oct 14.

  PMID: 19684472 BACKGROUND

• Einstein MH, Baron M, Levin MJ, Chatterjee A, Fox B, Scholar S, Rosen J, Chakhtoura N, Meric D, Dessy FJ, Datta SK, Descamps D, Dubin G; HPV-010 Study Group. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years. Hum Vaccin. 2011 Dec;7(12):1343-58. doi: 10.4161/hv.7.12.18281. Epub 2011 Dec 1.

  PMID: 22048173 BACKGROUND

• Einstein MH, Baron M, Levin MJ, Chatterjee A, Fox B, Scholar S, Rosen J, Chakhtoura N, Lebacq M, van der Most R, Moris P, Giannini SL, Schuind A, Datta SK, Descamps D; HPV-010 Study Group. Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years. Hum Vaccin. 2011 Dec;7(12):1359-73. doi: 10.4161/hv.7.12.18282. Epub 2011 Dec 1.

  PMID: 22048172 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

• Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology . 121:S1-S9.

  BACKGROUND

• Einstein MH, Levin MJ, Chatterjee A, Chakhtoura N, Takacs P, Catteau G, Dessy FJ, Moris P, Lin L, Struyf F, Dubin G; HPV-010 Study Group. Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: follow-up through Month 48 in a Phase III randomized study. Hum Vaccin Immunother. 2014;10(12):3455-65. doi: 10.4161/hv.36117.

  PMID: 25483700 BACKGROUND

• Einstein MH, Takacs P, Chatterjee A, Sperling RS, Chakhtoura N, Blatter MM, Lalezari J, David MP, Lin L, Struyf F, Dubin G; HPV-010 Study Group. Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: end-of-study analysis of a Phase III randomized trial. Hum Vaccin Immunother. 2014;10(12):3435-45. doi: 10.4161/hv.36121.

  PMID: 25483701 BACKGROUND

• Schwarz TF, Kocken M, Petaja T, Einstein MH, Spaczynski M, Louwers JA, Pedersen C, Levin M, Zahaf T, Poncelet S, Hardt K, Descamps D, Dubin G. Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Hum Vaccin. 2010 Dec;6(12):1054-61. doi: 10.4161/hv.6.12.13399. Epub 2010 Dec 1.

  PMID: 21157180 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

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; Virus Diseases

Interventions

human papillomavirus vaccine, L1 type 16, 18; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; 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

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2007
• First Posted: January 17, 2007
• Study Start: January 24, 2007
• Primary Completion: March 7, 2008
• Study Completion: May 14, 2012
• Last Updated: January 2, 2020
• Results First Posted: August 25, 2010

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 (40)