Last updated: 07/17/2024 15:13:41
Immunogenicity of GlaxoSmithKline Biological’s Human Papillomavirus (HPV) vaccine (580299) versus Merck’s Gardasil® in healthy females 18-45 years of age
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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.]
Trial description: 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.
Primary purpose:
Prevention
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
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:
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
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
Titers of Antibodies to Other Oncogenic HPV Types measured by Neutralization Assay
Timeframe: 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
Timeframe: 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)
Timeframe: At Month 6, 7, 12, 18, 24, 36, 48 and 60
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
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
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
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
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
Number of HPV-16 and HVP-18 specific B-cells per million B cells
Timeframe: At Month 7, 12, 18, 24, 36 and 48
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
Number of subjects completing the 3-dose vaccination schedule
Timeframe: Up to Month 7
Number of subjects reporting any, Grade 3 and related solicited local symptoms
Timeframe: During the 7-day period (Day 0-6) following vaccination
Number of subjects reporting any, Grade 3 and related solicited general symptoms
Timeframe: During the 7-day period (Day 0-6) following vaccination
Number of subjects with any, Grade 3 and related unsolicited adverse events (AEs)
Timeframe: During the 30-day period (Day 0-29) following vaccination
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up to Month 7
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up To Month 12
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up To Month 18
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up To Month 24
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up To Month 36
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up to Month 48
Number of subjects reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
Timeframe: Up to Month 60
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 7
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 12
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 18
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 24
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 36
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 48
Number of subjects with any, Grade 3 and related serious adverse events (SAEs)
Timeframe: Up to Month 60
Interventions:
Biological/vaccine: GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM)
Biological/vaccine: Gardasil ® (Merck & Co. Inc)
Biological/vaccine: Placebo
Enrollment:
1106
Observational study model:
Not applicable
Primary completion date:
2008-07-03
Time perspective:
Not applicable
Clinical publications:
Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology. 121:S1–S9.
Einstein M et al. (2009) 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. 5(10):705-719.
Einstein M et al. (2011) 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. 7(12):1343-1358.
Einstein MH et al. (2011) 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. 7(12):1359-1373.
Verstraeten T et al. (2008) Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 26(51):6630–6638.
Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology . 121:S1–S9.
Einstein MH et al. (2014) 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. 10(12):3455-3465.
Einstein MH et al. (2014) 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. 10(12):3435-3445.
Schwarz TF et al. (2010) Correlation between Levels of Human Papillomavirus (HPV)-16 and -18 Antibodies in Serum and Cervicovaginal Secretions in Girls and Women Vaccinated with HPV-16/18 AS04-Adjuvanted Vaccine. Hum Vaccin. 6(12):1054-1061.
Medical condition
Infections, Papillomavirus
Product
SB580299
Collaborators
Not applicable
Study date(s)
January 2007 to May 2012
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
18 - 45 years
Accepts healthy volunteers
Yes
- 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.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Arkansas City, Kansas, United States, 67005
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30342
Status
Study Complete
Location
GSK Investigational Site
Aurora, Colorado, United States, 80045
Status
Study Complete
Location
GSK Investigational Site
Bardstown, Kentucky, United States, 40004
Status
Study Complete
Location
GSK Investigational Site
Boynton Beach, Florida, United States, 33437
Status
Study Complete
Location
GSK Investigational Site
Carnegie, Pennsylvania, United States, 15106
Status
Study Complete
Location
GSK Investigational Site
Chandler, Arizona, United States, 85224
Status
Study Complete
Location
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27514
Status
Study Complete
Location
GSK Investigational Site
Chaska, Minnesota, United States, 55318
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45249
Status
Study Complete
Location
GSK Investigational Site
Coral Gables, Florida, United States, 33134
Status
Study Complete
Location
GSK Investigational Site
Erie, Pennsylvania, United States, 16507
Status
Study Complete
Location
GSK Investigational Site
Erie, Pennsylvania, United States, 16508
Status
Study Complete
Location
GSK Investigational Site
Fort Worth, Texas, United States, 76104
Status
Study Complete
Location
GSK Investigational Site
Lancaster, Pennsylvania, United States, 17601
Status
Study Complete
Location
GSK Investigational Site
Louisville, Colorado, United States, 80027
Status
Study Complete
Location
GSK Investigational Site
Milford, Massachusetts, United States, 01757
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84109
Status
Study Complete
Location
GSK Investigational Site
San Diego, California, United States, 92123
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94115
Status
Study Complete
Location
GSK Investigational Site
St. Paul, Minnesota, United States, 55108
Status
Study Complete
Location
GSK Investigational Site
Stevensville, Michigan, United States, 49127
Status
Study Complete
Location
GSK Investigational Site
Tacoma, Washington, United States, 98418
Status
Study Complete
Location
GSK Investigational Site
Upper St. Clair, Pennsylvania, United States, 15241
Status
Study Complete
Location
GSK Investigational Site
Vista, California, United States, 92083
Status
Study Complete
Location
GSK Investigational Site
Walla Walla, Washington, United States, 99362
Status
Study Complete
Location
GSK Investigational Site
Warwick, Rhode Island, United States, 02886
Status
Study Complete
Location
GSK Investigational Site
Wenatchee, Washington, United States, 98801
Status
Study Complete
Location
GSK Investigational Site
West Covina, California, United States, 91790
Status
Study Complete
Location
GSK Investigational Site
Willoughby Hills, Ohio, United States, 44094
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-07-03
Actual study completion date
2012-14-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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