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.
This Protocol Posting has been updated following Protocol Amendment 25, November 2010
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
1,106
Three doses administered intramuscularly at months 0, 1 and 6
Three doses administered intramuscularly at months 0, 2 and 6
One dose administered intramuscularly at month 1 to maintain blinding
One dose administered intramuscularly at month 2 to maintain blinding
GSK Investigational Site
Chandler, Arizona, United States
GSK Investigational Site
San Diego, California, United States
GSK Investigational Site
San Francisco, California, United States
GSK Investigational Site
Vista, California, United States
GSK Investigational Site
West Covina, California, United States
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.
Time frame: At Month 7
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Neutralizing Antibodies
Titers are given as Geometric Mean Titers (GMTs). Titer is the serum dilution giving a 50 percent reduction of the signal compared to a control without serum. Data for Month 7 on subjects aged 18 to 26 years are given in the outcome above as a primary outcome measure.
Time frame: 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
Other oncogenic HPV types include HPV-31 and HPV-45. The titer value (=serum dilution giving a 50 percent reduction of the signal compared to a control without serum) used as the cut-off for seroconversion was 40 for both other oncogenic types HPV-31 and HPV-45.
Time frame: At Month 7
Titers of Antibodies to Other Oncogenic HPV Types Measured by Neutralization Assay
Other Oncogenic Types include HPV-31 and HPV-45. Titers were measured by neutralization assay and are given 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
Time frame: 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
The titer value (=serum dilution giving a 50 percent reduction of the signal compared to a control without serum) used as the cut-off for seroconversion was 40 for both HPV-16 and HPV-18.
Time frame: 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)
Cut-off values assessed were greater than or equal to 8 ELISA units per milliliter (EL.U/mL) for HPV-16 and greater than or equal to 7 EL.U/mL for HPV-18.
Time frame: 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)
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: 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)
Other oncogenic types include HPV-31 and HPV-45. Cut-off values assessed were greater than or equal 59 EL.U/mL in the sera of subjects seronegative before vaccination.
Time frame: 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)
Other oncogenic types include HPV-31 and HPV-45. Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: 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
Number of cells were expressed as geometric mean, minimum and maximum values of specific CD4 cells producing at least 2 cytokines (CD40 Ligand, Interleukin-2, Tumor Necrosis Factor Alpha or Interferon-gamma) per million of CD4 T-cells.
Time frame: 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
Data were expressed as geometric mean, minimum and maximum values of specific CD8 cells producing at least 2 cytokines (CD40 Ligand, Interleukin-2, Tumor Necrosis Factor Alpha or Interferon-gamma) per million of CD8 T-cells. Analyses for further time points were not performed, as there was no response at these time points.
Time frame: At Month 7, 12 and 18
Number of HPV-16 and HVP-18 Specific B-cells Per Million B Cells
HPV-16 and HPV-18 Specific Memory B Cells were measured by Enzyme-linked immunosorbent spot (ELISPOT) assay and expressed as geometric mean, minimum and maximum values of specific B-cells per million of cells.
Time frame: 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)
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: At Month 7, 12, 18, 24, 36 and 48
Number of Subjects Completing the 3-dose Vaccination Schedule
Time frame: Up to Month 7
Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. All solicited local symptoms were assessed as related to study vaccination.
Time frame: During the 7-day period (Day 0-6) following vaccination
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], gastrointestinal, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time frame: During the 7-day period (Day 0-6) following vaccination
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.Grade 3 AE = AE that prevented normal activity. Related AE = AE assessed by the investigator as causally related to the study vaccination.
Time frame: 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)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSCs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up to Month 7
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up To Month 12
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up To Month 18
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up To Month 24
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up To Month 36
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSCs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up to Month 48
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs)
NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSCs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. Note: NOCD and MSC cases were unblinded at the Month 60 analysis.
Time frame: Up to Month 60
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 7
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 12
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 18
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 24
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 36
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAEs was not assessed.
Time frame: Up to Month 48
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccination. Intensity of SAE(s) was not assessed. Note: SAEs were unblinded at the Month 60 analysis.
Time frame: Up to Month 60
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GSK Investigational Site
Aurora, Colorado, United States
GSK Investigational Site
Louisville, Colorado, United States
GSK Investigational Site
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Coral Gables, Florida, United States
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Miami, Florida, United States
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