Clinical trial NCT00423046: Immunogenicity of GlaxoSmithKline Biological's Human Papillomavirus (HPV) Vaccine (580299) Versus Merck's Gardasil® in Healthy Females 18-45 Years of Age
Official title: Phase IIIb, Observer-blind Study to Compare Immunogenicity of GSK Biologicals' HPV-16/18 L1/AS04 Vaccine Versus Gardasil® [Quadrivalent Human Papillomavirus (HPV-6,11,16,18 L1 VLP) Recombinant Vaccine Merck & Co., Inc.]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Papillomavirus Vaccines
Keywords: Vaccines
Cervical cancer
Immunogenicity
Humans
Safety
Viral infections
Human papillomavirus (HPV)
Comparative study
Human papillomavirus vaccine
Adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-01-17
Enrollment: 1106
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: This Protocol Posting has been updated following Protocol Amendment 25, November 2010

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Neutralizing Antibodies
timeFrame: At Month 7
Secondary outcomes:
measure: Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Neutralizing Antibodies
timeFrame: At Month 6, 7, 12, 18, 24, 36, 48 and 60
measure: Number of Subjects With Antibody Titers (Neutralizing Assay) Against Other Oncongenic HPV Types Greater Than or Equal to the Cut-off Value
timeFrame: At Month 7
measure: Titers of Antibodies to Other Oncogenic HPV Types Measured by Neutralization Assay
timeFrame: At Month 7
measure: 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
timeFrame: At Month 6, 7, 12, 18, 24, 36, 48 and 60
measure: 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)
timeFrame: At Month 6, 7, 12, 18, 24, 36, 48 and 60
measure: Titers of Anti-HPV-16 and Anti-HPV-18 Immunoglobulin G (IgG) Antibodies Measured by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: At Month 6, 7, 12, 18, 24, 36, 48 and 60
measure: Number of Subjects With Antibody Titers to Other Oncogenic HPV Types Greater Than or Equal to a Cut-off Value, Measured by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: At Month 6, 7, 12, 18, 24, 36 and 48
measure: Titers of Antibodies to Other Oncogenic HPV Types Measured by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: At Month 6, 7, 12, 18, 24, 36 and 48
measure: Number of HPV-16 and HVP-18 Specific CD4 Cells Producing at Least 2 Different Cytokines Per Million of CD4 T Cells
timeFrame: At Month 7, 12, 18, 24, 36 and 48
measure: Number of HPV-16 and HVP-18 Specific CD8 Cells Producing at Least 2 Different Cytokines Per Million of CD8 T Cells
timeFrame: At Month 7, 12 and 18
measure: Number of HPV-16 and HVP-18 Specific B-cells Per Million B Cells
timeFrame: At Month 7, 12, 18, 24, 36 and 48
measure: Titers of HPV-16 IgG and HPV-18 IgG (by ELISA) in Cervico-vaginal Secretions (CVS)
timeFrame: At Month 7, 12, 18, 24, 36 and 48
measure: Number of Subjects Completing the 3-dose Vaccination Schedule
timeFrame: Up to Month 7
measure: Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms
timeFrame: During the 7-day period (Day 0-6) following vaccination
measure: Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day period (Day 0-6) following vaccination
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day period (Day 0-29) following vaccination
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up to Month 7
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up To Month 12
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up To Month 18
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up To Month 24
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up To Month 36
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up to Month 48
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
timeFrame: Up to Month 60
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 7
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 12
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 18
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 24
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 36
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 48
measure: Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
timeFrame: Up to Month 60
Other outcomes:
Locations:
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Vista
country: United States
facility: GSK Investigational Site
state: California
city: West Covina
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Louisville
country: United States
facility: GSK Investigational Site
state: Colorado
city: Boynton Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Coral Gables
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Boise
country: United States
facility: GSK Investigational Site
state: Idaho
city: Arkansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Bardstown
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Milford
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Stevensville
country: United States
facility: GSK Investigational Site
state: Michigan
city: Chaska
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Paul
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Willoughby Hills
country: United States
facility: GSK Investigational Site
state: Ohio
city: Carnegie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Erie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Erie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Lancaster
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Upper Saint Clair
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Warwick
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Walla Walla
country: United States
facility: GSK Investigational Site
state: Washington
city: Wenatchee
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology. 121:S1-S9.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology . 121:S1-S9.
citation: 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.
citation: 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.
citation: 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.