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Cervarix

Phase 3

Human Papillomavirus (HPV) Infection | Monoclonal antibody | Infectious Disease |GSK plc|Last Updated: Nov 17, 2020

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment676

FDA Designations

No designations recorded

Clinical trial landscape

Cervarix · 18 trials · 5 indications

Phase 3 12Phase 2 5Phase 1 1
NCT01627561Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years OldInfections, Papillomavirus
COMPLETED148 Analytics
NCT01462357Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old FemalesInfections, Papillomavirus
COMPLETED1,079 Analytics
NCT01190176Gynaecological Follow-up of a Subset of HPV-015 (NCT00294047) Study SubjectsInfections, Papillomavirus
COMPLETED34 Analytics
NCT00811798Safety Study of GSK Biologicals' HPV Vaccine (GSK-580299) in Healthy Female Subjects.Infections, Papillomavirus
COMPLETED92 Analytics
NCT00578227Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus Vaccine With Another Vaccine in Healthy Female SubjectsInfections, Papillomavirus
COMPLETED814 Analytics
NCT00481767Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV) Vaccine (GSK580299) in Healthy Female Subjects 10-25 Years of Age.Human Papillomavirus (HPV) Infection
COMPLETED676 Analytics
NCT00492544Immunogenicity and Safety of GSK Biologicals' HPV Vaccine 580299 in Healthy Japanese Females 10-15 Years of AgeInfections, Papillomavirus
COMPLETED100 Analytics
NCT00337818Human Papillomavirus (HPV) Vaccine Consistency and Non-inferiority Trial in Young Adult WomenPapillomavirus Type 16/18 Infection
COMPLETED770 Analytics
NCT00294047Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and OlderInfections, Papillomavirus
COMPLETED5,752 Analytics
NCT00250276Evaluation of the Immune Responses of GSK Biologicals' HPV Vaccine Following Manufacturing Process Adaptation.Infections, Papillomavirus
COMPLETED798 Analytics
PHASE3COMPLETED
Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Gynaecological Follow-up of a Subset of HPV-015 (NCT00294047) Study Subjects
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Safety Study of GSK Biologicals' HPV Vaccine (GSK-580299) in Healthy Female Subjects.
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus Vaccine With Another Vaccine in Healthy Female Subjects
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV) Vaccine (GSK580299) in Healthy Female Subjects 10-25 Years of Age.
Human Papillomavirus (HPV) InfectionUnlock trial analytics
PHASE3COMPLETED
Immunogenicity and Safety of GSK Biologicals' HPV Vaccine 580299 in Healthy Japanese Females 10-15 Years of Age
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Human Papillomavirus (HPV) Vaccine Consistency and Non-inferiority Trial in Young Adult Women
Papillomavirus Type 16/18 InfectionUnlock trial analytics
PHASE3COMPLETED
Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older
Infections, PapillomavirusUnlock trial analytics
PHASE3COMPLETED
Evaluation of the Immune Responses of GSK Biologicals' HPV Vaccine Following Manufacturing Process Adaptation.
Infections, PapillomavirusUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses

Assessed solicited general symptoms were arthralgia (only in joints which were distal from the injection site), drowsiness, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, irritability/fussiness, loss of appetite, myalgia, rash (not urticaria, not measels/rubella-like rash), 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. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Related = symptom assessed by the investigator as causally related to the study vaccination.

Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) Reported During the 43-day Period Following the Vaccination at Day 0
During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0

An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related AE = AE assessed by the investigator as causally related to the study vaccination.

Number of Subjects With Any, Grade 3 and Related Unsolicited AEs Reported During the 30-day Period Following the Vaccination at Month 6
During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6

An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related AE = AE assessed by the investigator as causally related to the study vaccination.

Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Day 42 by Baseline Ranges
At Day 42 (i.e. 42 days after the vaccination at Day 0)

The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes \[white blood cells\] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Day 42 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) \[e.g. ALAT Below (baseline) - Within (Day 42) = ALAT with below normal value at baseline and within normal values at Day 42\].

Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Month 7 by Baseline Ranges
At Month 7 (i.e. 30 days after the vaccination at Month 6)

The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes \[white blood cells\] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Month 7 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) \[e.g. ALAT Below (baseline) - Within (Month 7) = ALAT with below normal value at baseline and within normal values at Month 7\].

Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to Month 7
From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)

SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.

Number of Subjects With AEs and SAEs Leading to Withdrawal From Day 0 up to Month 7
From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)

The number of subjects with AEs and SAEs leading to premature discontinuation of the study was assessed.

Number of Subjects With Potential Immune-mediated Diseases (pIMDs) From Day 0 up to Month 7
From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)

pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology.

Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)

MSCs were defined as AEs prompting emergency room or physician visits that were not related to common diseases or were not routine visits for physical examination or vaccination and as SAEs that were not related to common diseases. Common diseases included: upper respiratory tract infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.

Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7
At Month 7 (i.e. 30 days after the vaccination at Month 6)

Seroconversion was defined as a titer greater than or equal to the cut-off value in the serum of seronegative subjects, defined as subjects who had an antibody titer below the cut-off value before vaccination. Titers were measured by Enzyme Linked Immunosorbent Assay (ELISA) and the cut-offs were 19 ELISA Units per milliliter (EU/mL) for HPV-16 and 18 EU/mL for HPV-18.

Anti-HPV-16/18 Antibody Concentrations at Month 7
At Month 7 (i.e. 30 days after the vaccination at Month 6)

Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EU/mL.

Number of Seroconverted Subjects for Anti-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity
At Month 7 (i.e. one month after the last dose of study vaccine)

Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers greater than or equal to (≥) 19 and 18 ELISA units per milliliter (EL.U/mL), respectively), in the serum of subjects seronegative before vaccination.

Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the ATP Cohort for Immunogenicity
At Month 7 (i.e. one month after the last dose of study vaccine)

Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the Total Vaccinated Cohort (TVC)
At Month 7 (i.e. one month after the last dose of study vaccine)

Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

Number of Subjects Reporting Positive Oncogenic HPV DNA Results by Hybrid Capture II Test (HCII) at Month 12
At Month 12 [12 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Subjects with 2 positive oncogenic HPV DNA tests or 1 cervical cytology reading ≥ASC-US (atypical squamous cells of undetermined significance) positive for oncogenic HPV DNA or 1 cervical cytology reading ≥LSIL (low grade squamous intraepithelial lesion) were referred for colposcopy evaluation according to the clinical management algorithm.

Number of Subjects Reporting Positive Oncogenic HPV DNA Results by Hybrid Capture II Test (HCII) at Month 24
At Month 24 [24 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Subjects with 2 positive oncogenic HPV DNA tests or 1 cervical cytology reading ≥ASC-US (atypical squamous cells of undetermined significance) positive for oncogenic HPV DNA or 1 cervical cytology reading ≥LSIL (low grade squamous intraepithelial lesion) were referred for colposcopy evaluation according to the clinical management algorithm.

Number of Subjects Reporting Positive Oncogenic HPV DNA Results by Hybrid Capture II Test (HCII) at Month 36
At Month 36 [36 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Subjects with 2 positive oncogenic HPV DNA tests or 1 cervical cytology reading ≥ASC-US (atypical squamous cells of undetermined significance) positive for oncogenic HPV DNA or 1 cervical cytology reading ≥LSIL (low grade squamous intraepithelial lesion) were referred for colposcopy evaluation according to the clinical management algorithm.

Number of Subjects Reporting Positive Oncogenic HPV DNA Results by Hybrid Capture II Test (HCII) at Month 48
At Month 48 [48 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Subjects with 2 positive oncogenic HPV DNA tests or 1 cervical cytology reading ≥ASC-US (atypical squamous cells of undetermined significance) positive for oncogenic HPV DNA or 1 cervical cytology reading ≥LSIL (low grade squamous intraepithelial lesion) were referred for colposcopy evaluation according to the clinical management algorithm.

Number of Subjects With Any Cytological Abnormalities in Cervical Samples by ThinPrep PapTest at Month 12
At Month 12 [12 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Cervical cytology was performed using the ThinPrep PapTest by Quest Diagnostics, or another GSK designated laboratory. Cervical cells for ThinPrep cytology were collected using the sampling device provided and rinsed into a collection vial containing PreservCyt medium.

Number of Subjects With Any Cytological Abnormalities in Cervical Samples by ThinPrep PapTest at Month 24
At Month 24 [24 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Cervical cytology was performed using the ThinPrep PapTest by Quest Diagnostics, or another GSK designated laboratory. Cervical cells for ThinPrep cytology were collected using the sampling device provided and rinsed into a collection vial containing PreservCyt medium.

Number of Subjects With Any Cytological Abnormalities in Cervical Samples by ThinPrep PapTest at Month 36
At Month 36 [36 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Cervical cytology was performed using the ThinPrep PapTest by Quest Diagnostics, or another GSK designated laboratory. Cervical cells for ThinPrep cytology were collected using the sampling device provided and rinsed into a collection vial containing PreservCyt medium.

Number of Subjects With Any Cytological Abnormalities in Cervical Samples by ThinPrep PapTest at Month 48
At Month 48 [48 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Cervical cytology was performed using the ThinPrep PapTest by Quest Diagnostics, or another GSK designated laboratory. Cervical cells for ThinPrep cytology were collected using the sampling device provided and rinsed into a collection vial containing PreservCyt medium.

Number of Subjects With Referral to Colposcopy at Month 12
At Month 12 [12 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Number of Subjects With Referral to Colposcopy at Month 24
At Month 24 [24 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Number of Subjects With Referral to Colposcopy at Month 36
At Month 36 [36 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Number of Subjects With Referral to Colposcopy at Month 48
At Month 48 [48 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Number of Subjects With Referral to Treatment at Month 12
At Month 12 [12 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

If a high-grade lesion was observed, the subject was referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was handled according to local medical practice within the local health care system. After treatment, the subject's participation in the study ended.

Number of Subjects With Referral to Treatment at Month 24
At Month 24 [24 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

If a high-grade lesion was observed, the subject was referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was handled according to local medical practice within the local health care system. After treatment, the subject's participation in the study ended.

Number of Subjects With Referral to Treatment at Month 36
At Month 36 [36 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

If a high-grade lesion was observed, the subject was referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was handled according to local medical practice within the local health care system. After treatment, the subject's participation in the study ended.

Number of Subjects With Referral to Treatment at Month 48
At Month 48 [48 months post concluding HPV-015 visit (Visit 9, Visit 11 or last HPV-015 study visit)]

If a high-grade lesion was observed, the subject was referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was handled according to local medical practice within the local health care system. After treatment, the subject's participation in the study ended.

Number of Subjects Reporting Any Serious Adverse Event (SAE) and SAE(s) With a Causal Relationship to Vaccination as Assessed by the Investigator.
During the entire study period (Day 0 up to the telephone contact at Month 12).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies
At Month 7

Seroconversion is defined as the appearance of anti-HAV antibodies \[i.e., antibody titer greater than or equal to 15 milli-international units/milliliter (mIU/mL)\] in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.

Anti-Heptatis A (HAV) Antibody Titers.
At Month 7

Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.

Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
At Month 7

A subject seroprotected against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.

Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
At Month 7

Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers
At Month 7

Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

Number of Seroconverted Subjects for Anti-human Papillomavirus (HPV)-16 and 18 Antibodies
At Month 7

A seroconverted subject was a subject with antibody titers below 8 or 7 Enzyme-linked Immunosorbent Assay Units per milliliter (EL.U/mL) for anti-HPV-16 and 18, respectively, before vaccination and antibody titers ≥ 8 or 7 EL.U/mL for anti-HPV-16 and 18, respectively, after vaccination. The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.

Geometric Mean Titers (GMTs) of Anti-HPV-16 and Anti-HPV-18 Antibodies
At Month 7

Titers were expressed as GMTs in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.

Anti-HPV-16 and Anti-HPV-18 Antibody Titers
Before vaccination (PRE) and one month post Dose 3 (Month 7)

Titers are given as geometric mean titers (GMTs) calculated on all subjects.

Number of Subjects Reporting Solicited Local Symptoms
During the 7-day (Days 0-6) period following each vaccination

Solicited local symptoms assessed include pain, redness and swelling.

Number of Subjects Reporting Solicited General Symptoms
During the 7-day (Days 0-6) period following each vaccination

Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
At months 18*, 24, 36 and 48

Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). \*Data for Month 18 outcome variables were incorporated into the Month 24 analyses.

Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.
Up to Month 48

CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) * Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).
Up to Month 48

CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). * Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Number of Seroconverted (SCR) Subjects for Anti-Human Papillomavirus Type 16 (Anti-HPV-16) and Anti-Human Papillomavirus Type 18 (Anti-HPV-18)
At Month 7

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 concentrations ≥8 Enzyme-Linked Immunosorbent Assay \[ELISA\] units per milliliter \[EL.U/mL\] and anti-HPV-18 concentrations ≥7 EL.U/mL) in the serum of subjects seronegative before vaccination.

Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18
At Month 7

Seropositivity defined subjects with anti-HPV-16 antibody concentration ≥ 8 EL.U/mL and/or anti-HPV-18 antibody concentration ≥ 7 EL.U/mL.

Number of Seroconverted Subjects for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, in Women 15 to 25 Years of Age and Women 26 to 45 Years of Age
At Month 7

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies \[i.e. antibody titer greater than or equal to (≥) the cut-off value\] in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Data for the Cervarix (46-55 Years) Group are presented in the Secondary Outcomes as per Protocol.

Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Months 18, 24, 36 and 48
At Months 18, 24, 36 and 48

Anti-HPV 16/18 antibody titers were detected in sera samples and presented as Geometric Mean Titers (GMT), expressed in EL.U/mL. Data for pre-vaccination, Month 2, Month 7 and Month 12 are presented in the Secondary Outcomes as per Protocol.

Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3

CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: 1. DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). 2. Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms
Within 7 days after each dose and across doses

Solicited local symptoms assessed were pain and swelling. Any = occurrence of any solicited local regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 50 millimeters (mm) of injection site. Solicited local symptoms were assessed as related to the study vaccination.

Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms
Within 7 days after each dose and across doses

Solicited general symptoms assessed 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 any solicited general symptom regardless of their intensity grade or relationship. Grade 3 Symptom = symptom that prevented normal activity. Grade 3 Urticaria = Urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as causally related to the vaccination.

Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms
Within 30 days after any vaccination

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

Number of Subjects Reporting Serious Adverse Events (SAEs) From Day 0 up to Month 7
From Day 0 up to Month 7

SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or a congenital anomaly/birth defect in the offspring of a study subject.

Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies From Day 0 up to Month 7
From Day 0 up to Month 7

The subjects with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies. The outcome of the reported pregnancy was a live infant with no apparent congenital anomaly.

Number of Subjects Reporting SAEs From Day 0 up to Month 12
From Day 0 up to Month 12

SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or a congenital anomaly/birth defect in the offspring of a study subject.

Number of Subjects With MSCs From Day 0 up to Month 12
From Day 0 up to Month 12

MSCs were collected regardless of causal relationship to vaccination and intensity. Medically significant conditions were defined as adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or serious adverse events (SAEs) that were 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.

Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies From Day 0 up to Month 12
From Day 0 up to Month 12

The subjects with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies. The outcome of the reported pregnancy was a live infant with no apparent congenital anomaly.

Number of Subjects Reporting Clinically Relevant Abnormalities in Red Blood Cells and Platelets Parameters at Day 7 and at Months 1, 2, 4, 6 and 7
At Day 7 and at Months 1, 2, 4, 6 and 7

Haematological laboratory parameters assessed were red blood cells (RBC) and platelets (PLA). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects Reporting Clinically Relevant Abnormalities in White Blood Cells and Neutrophils Parameters at Day 7 and Months 1, 2, 4, 6 and 7
At Day 7 and Months 1, 2, 4, 6 and 7

Haematological laboratory parameters assessed were white blood cells (WBC) and neutrophils (NEU). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects Reporting Clinically Relevant Abnormalities in Lymphocytes and Monocytes Parameters at Day 7 and Months 1, 2, 4, 6 and 7
At Day 7 and at Months 1, 2, 4, 6 and 7

Haematological laboratory parameters assessed were lymphocytes (LYM) and monocytes (MON). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects Reporting Clinically Relevant Abnormalities in Haemoglobin and Haematocrit Parameters at Day 7 and Months 1, 2, 4, 6 and 7
At Day 7 and Months 1, 2, 4, 6 and 7

Haematological laboratory parameters assessed were haemoglobin (Hgb) and haematocrit (Hct). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects With Clinically Relevant Abnormalities in Eosinophils, Basophils and Creatinine Parameters at Day 7 and Months 1, 2, 4, 6 and 7
At Day 7 and at Months 1, 2, 4, 6 and 7

Haematological and biochemical laboratory parameters assessed were eosinophils (EOS), basophils (BAS) and creatinine (CREA). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects With Clinically Relevant Abnormalities in Alanine Aminotransferase Parameter at Day 7 and Months 1, 2, 4, 6 and 7
At Day 7 and Months 1, 2, 4, 6 and 7

Biochemical laboratory parameter assessed was alanine aminotransferase (ALAT). By pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects Reporting Clinically Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells at Month 10 and Month 12
At Month 10 and Month 12

Haematological laboratory parameters assessed were neutrophils (NEU), platelets (PLA), red blood cells (RBC) and white blood cells (WBC). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Subjects With Clinically Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine, Eosinophils, Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters at Month 10 and Month 12
At Month 10 and Month 12

Haematological and biochemical laboratory parameters assessed were alanine aminotransferase (ALAT), basophils (BAS), creatinine (CREA), eosinophils (EOS), haematocrit (Hct), haemoglobin (Hgb), lymphocytes (LYM) and monocytes (MON). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated).

Number of Cluster of Differention 4 (CD4+) Cells Per Cubic Millimeter in All HIV+ Subjects at Pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
At pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7

The number of CD4+ cells per cubic millimeter (mm\^3) in all HIV+ subjects at pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7 is reported.

Number of CD4+ Cells Per Cubic Millimeter in All HIV+ Subjects at Month 10 and Month 12
At Month 10 and Month 12

The number of CD4+ cells per cubic millimeter (mm\^3) in all HIV+ subjects at Month 10 and Month 12 is reported.

HIV Viral Load in All HIV+ Subjects at Pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
At pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7

The viral load was calculated by estimating the amount of virus in blood samples and it was given in number of Ribonucleic acid copies per milliliter (in log10) \[RNA copies/mL (in log10)\].

HIV Viral Load in All HIV+ Subjects at Month 10 and Month 12
At Month 10 and Month 12

The viral load was calculated by estimating the amount of virus in blood samples and was given in number of RNA copies/mL (in log 10).

Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage by CD4+ Cell Count Category at Baseline in All HIV+ Subjects at Months 1, 2, 4, 6 and 7
At Months 1, 2, 4, 6 and 7

CD4+ cell count categories, at baseline, assessed were (i) below (\<) 200 CD4+ cells per cubic millimeter (mm\^3), (ii) between 200 and 500 CD4+ cells/mm\^3 and (iii) above 500 CD4+ cells/mm\^3. WHO classification of HIV-associated clinical disease: 1 = Asymptomatic HIV-associated symptoms = WHO clinical stage 1; 2 = Mild HIV-associated symptoms = WHO clinical stage 2; 3 = Advanced HIV-associated symptoms = WHO clinical stage 3; 4 = Severe HIV-associated symptoms = WHO clinical stage 4.

Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage by CD4+ Cell Count Category at Baseline in All HIV+ Subjects at Month 10 and Month 12
At Month 10 and Month 12

CD4+ cell count categories, at baseline, assessed were: (i) below (\<) 200 CD4+ cells per cubic millimeter (mm\^3), (ii) between 200 and 500 CD4+ cells/mm\^3 and (iii) above (\>) 500 CD4+ cells/mm\^3. WHO classification of HIV-associated clinical disease: 1 = Asymptomatic HIV-associated symptoms = WHO clinical stage 1; 2 = Mild HIV-associated symptoms = WHO clinical stage 2; 3 = Advanced HIV-associated symptoms = WHO clinical stage 3; 4 = Severe HIV-associated symptoms = WHO clinical stage 4.

Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies at Pre-vaccination (Day 0) and Months 2 and 7
At pre-vaccination (Day 0) and Months 2 and 7

Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 titers ≥ 8 EL.U/mL and anti-HPV-18 titers ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject whose antibody titers are below the cut-off value. Due to the high proportion of initially seropositive subjects in the study population, seroconversion rates were considered for all subjects in the According-to-Protocol (ATP) cohort for immunogenicity regardless of baseline serostatus.

Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies at Month 12
At Month 12

Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 titers ≥ 8 ELISA units per milliliter (EL.U/mL) and anti-HPV-18 titers ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject whose antibody titers are below the cut-off value. Due to the high proportion of initially seropositive subjects in the study population, seroconversion rates were considered for all subjects in the ATP cohort for immunogenicity regardless of baseline serostatus.

Concentrations for HPV-16 and HPV-18 Antibodies at Pre-vaccination (Day 0) and Months 2 and 7
At pre-vaccination (Day 0) and Months 2 and 7

Concentrations are expressed as geometric mean antibody concentrations (GMCs) and are given in EL.U/mL. The antibody concentrations against HPV-16 and HPV-18 were determined by Enzyme-linked immunosorbent assay (ELISA). The cut-off values of the assay are 8 EL.U/mL for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18.

Concentrations for HPV-16 and HPV-18 Antibodies at Month 12
At Month 12

Concentrations are expressed as geometric mean antibody concentrations (GMCs) and are given in EL.U/mL. The antibody concentrations against HPV-16 and HPV-18 were determined by Enzyme-linked immunosorbent assay (ELISA). The cut-off values of the assay are 8 EL.U/mL for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18.

Cell Mediated Immune (CMI) Response (B-cell Responses) Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Day 0
At pre-vaccination (Day 0)

The CMI response is expressed by the number of subjects with B-cell response to VLP-16 and VLP-18 above (\>) 0 as measured by Flow cytometry.

CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 2
At Month 2

The CMI response is expressed by the number of subjects with B-cell response to VLP-16 and VLP-18 above (\>) 0 as measured by Flow cytometry.

CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 7
At Month 7

The CMI response is expressed by the number of subjects with B-cell response to VLP-16 and VLP-18 above (\>) 0 as measured by Flow cytometry.

CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 12
At Month 12

The CMI response is expressed by the number of subjects with B-cell response to VLP-16 and VLP-18 above (\>) 0 as measured by Flow cytometry.

CMI Response (T-cell Responses) Related to HPV-16 and HPV-18 Measured by Intracellular Cytokine Staining (ICS)
At pre-vaccination (Day 0) and at Months 2, 7 and 12

The CMI response is the measure of the cytokines production \[i.e. Cluster of Differentiation 40 Ligand (CD40L), Interferon gamma (IFN-γ), interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α)\] by HPV-antigen specific T lymphocytes and measured by Intracellular Cytokine Staining (ICS) assay. The results were expressed as a frequency of positive CD4 or CD8 T-cell producing at least 1 cytokine within the CD4 or CD8 T-cell sub-population. All doubles = T cell expressing at least 2 cytokines.

Number of Subjects With Anti-human Papilloma Virus-16 (Anti-HPV-16) and Anti-HPV-18 Antibody Titers Greater Than or Equal to Pre-defined Cut-off Values
At Day 7 and Month 1 (Day 30)

Cut-off values assessed include 8 Enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18
Up to year 8

Cervical HPV infection was defined as the first detection of an HPV type in a subject previously negative for that HPV type.

Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and /or HPV-18
Up to year 7

Cervical HPV infection was defined as the first detection of an HPV type in a subject previously negative for that HPV type.

Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18
At Month 7

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies \[anti-HPV-16 titers greater than or equal to (≥) 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 titres ≥7 EL.U/mL\] in the serum of subjects seronegative before vaccination.

Antibody Titers Against HPV-16 (Anti-HPV-16) and HPV-18 (Anti-HPV-18)
At Month 7

Titers were presented as geometric mean titers (GMT).

Cervical infection with HPV-16 and/or HPV-18
Throughout the study
Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7).

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms
Within 7 days (Day 0-6) after vaccination.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the solicited local symptom irrespective of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling larger than (\>) 50 millimeters (mm).

Secondary Endpoints

Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Number of Seropositive Subjects for Measles Antigen
At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposePREVENTION

Treatment Arms

ArmTypeDescription
Cervarix GroupEXPERIMENTALHealthy female subjects aged between, and including, 4 and 6 years, who received two doses of Cervarix vaccine at Day 0 and Month 6, administered intramuscularly in the deltoid muscle of the left upper arm.
Priorix + Infanrix GroupACTIVE_COMPARATORHealthy female subjects aged between, and including, 4 and 6 years, who received one dose of Priorix vaccine at Day 0 and one dose of Infanrix vaccine at Month 6, administered intramuscularly in the deltoid muscle of the left upper arm.
Cervarix 2 dose GroupEXPERIMENTALSubjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Gardasil 2 dose GroupEXPERIMENTALSubjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Gardasil 3 dose GroupEXPERIMENTALSubjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
HPV-062 study subjects GroupEXPERIMENTALHPV-015 (NCT00294047) study subjects who had normal cervical cytology, but tested positive for oncogenic HPV infection at their concluding HPV-015 (NCT00294047) study visit or were pregnant, so that no cervical sample could be collected at their concluding HPV-015 (NCT00294047) study visit.
Cervarix™ & Twinrix™ GroupEXPERIMENTALSubjects received 3 doses of Human Papilloma Virus (HPV) vaccine co-administered with combined Hepatitis A \& Hepatitis B (HAB) vaccine (Months 0, 1 \& 6).
Cervarix™ GroupEXPERIMENTALSubjects received 3 doses of HPV vaccine (Months 0, 1 \& 6).
Twinrix™ GroupACTIVE_COMPARATORSubjects received 3 doses of HAB vaccine (Months 0, 1 \& 6).
Placebo GroupPLACEBO_COMPARATORHealthy female subjects who received 3 doses of placebo at Months 0, 1 and 6, administered intramuscularly into the deltoid region of the non-dominant arm. For some analyses the group was stratified by age into a 10-14 years of age group and a 15-25 years of age group.
CervarixEXPERIMENTALSubjects received 3 doses of Cervarix™ (HPV-16/18 L1 VLP AS04) according to a 0, 1, 6-month schedule.
Cervarix New ProcessEXPERIMENTALSubjects aged 15 to 25 years received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus \[HPV\]) produced with the new manufacturing process.
Cervarix Old Process GroupEXPERIMENTALSubjects aged 15 to 25 years who received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus \[HPV\]) produced with the old manufacturing process.
Cervarix Young/Lot 1 GroupEXPERIMENTALSubjects aged 10 to 14 years, who received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus \[HPV\]) produced with the new manufacturing process (Lot 1).
Aluminium Hydroxide GroupPLACEBO_COMPARATORSubjects 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.
Cervarix Lot1 GroupEXPERIMENTALSubjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 1 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.
Cervarix Lot2 GroupEXPERIMENTALSubjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 2 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.
Cervarix Lot3 GroupEXPERIMENTALSubjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 3 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.
Cervarix Low GroupEXPERIMENTALSubjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine manufactured lower scale-80L according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.
Cervarix (15-25 Years) GroupEXPERIMENTALWomen aged 15 to 25 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Cervarix (26-45 Years) GroupEXPERIMENTALWomen aged 26 to 45 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Cervarix (46-55 Years) GroupEXPERIMENTALWomen aged 46 to 55 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule.
Havrix GroupACTIVE_COMPARATORSubjects received 3 doses of GSK Biologicals' hepatitis A vaccine \[HAV\] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
HIV+/Cervarix GroupEXPERIMENTALHuman immunodeficiency virus positive (HIV+) female subjects who received 3 doses of Cervarix vaccine administrated by intramuscular injection into the deltoid region of the non-dominant arm, according to a 0, 1, 6-month schedule.
HIV+/Aluminium Hydroxide GroupACTIVE_COMPARATORHuman immunodeficiency virus positive (HIV+) female subjects who received 3 doses of control Aluminium Hydroxide \[Al(OH)3\], administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule.
HIV-/Cervarix GroupEXPERIMENTALHuman immunodeficiency virus negative (HIV-) subjects who received 3 doses of Cervarix vaccine administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule.
Cervarix™ 4-Dose GroupEXPERIMENTALSubjects who had received 3 doses of Cervarix™ in study 580299/001 (NCT00689741), received a 4th dose of Cervarix™ on Day 0 in the current study.
Cervarix™ 3-Dose GroupEXPERIMENTALSubjects who had received 3 doses of placebo in study 580299/001 (NCT00689741), received 3 doses of Cervarix™ (Day 0, Month 1 and Month 6) in the current study.
Engerix-B GroupACTIVE_COMPARATORHealthy male subjects between and including 10 to 18 years of age at the time of the first vaccination, who were administered 3 doses of Engerix-B™ (HBV) vaccine, intramuscularly into the deltoid region of the non-dominant arm, according to a 0, 1 and 6-month schedule. The subjects were followed up for 7 months after the first dose and an additional telephone contact was foreseen at Month 12.
AEXPERIMENTAL -
BPLACEBO_COMPARATOR -
Cervarix 1/Placebo GroupEXPERIMENTALSubjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 2, and 1 dose of placebo at Month 6. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Cervarix 1/Placebo/Cervarix 1 GroupEXPERIMENTALSubjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Cervarix 2/Placebo/Cervarix 2 GroupEXPERIMENTALSubjects received 2 doses of the Cervarix vaccine, formulation 2, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.
Cervarix 2 GroupEXPERIMENTALSubjects received 3 doses of the Cervarix vaccine, formulation 2, at Month 0, Month 2 and Month 6. The Cervarix vaccine was administered intramuscularly into the deltoid of the non-dominant arm.

Interventions

NameTypeDescription
CervarixBIOLOGICAL2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6.
PriorixBIOLOGICAL1 dose administered intramuscularly in the deltoid muscle of the left arm at Day 0.
InfanrixBIOLOGICAL1 dose administered intramuscularly in the deltoid muscle of the left arm at Month 6.
GardasilBIOLOGICAL2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gardasil 2 dose Group) or at Day 0, Month 2 and Month 6 (Gardasil 3 dose Group), respectively.
PlaceboDRUG2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding.
Gynaecological follow-upPROCEDURESubjects will receive a gynaecological follow-up with cytology and oncogenic HPV DNA testing every 12 months, for up to a maximum of four years.
Placebo controlBIOLOGICALSubjects received 3 doses of the control \[Al(OH)3\] administered intramuscularly according to a 0, 1, 6 month vaccination schedule in the primary study HPV-015.
Cervarix™BIOLOGICALThree doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Twinrix ™ PaediatricBIOLOGICALThree doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Placebo Al(OH)3DRUGPlacebo was administered according to a 0, 1 and 6-month schedule, intramuscularly into the deltoid region of the non-dominant arm.
Cervarix™ (HPV-16/18 L1 VLP AS04)BIOLOGICALThree doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
Havrix™-based investigational formulationBIOLOGICALIntramuscular injection, 3 doses
Blood samplingPROCEDUREBlood sampling at Visit 3, 5 and 7.
Collection of cervical specimenPROCEDURECollection of cervical specimen at Visit2, 3, 4, 5, 6 and 7.
Cervarix vaccineBIOLOGICALAll subjects received an intramuscular injection into the deltoid of the non-dominant arm according to a 0, 1 and 6-month schedule.
Engerix-B vaccineBIOLOGICALAll subjects received an intramuscular injection into the deltoid of the non-dominant arm according to a 0, 1 and 6-month schedule
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Eligibility Criteria

Age Range4 Years to 6 Years
SexFEMALE
Healthy VolunteersYes
Study Sites4

Inclusion Criteria: * Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol. * A female between, and including, 4 and 6 years of age at the time of the first vaccination. * Written informed con...

Countries:ColombiaMexicoPanamaFranceHong KongSingaporeSwedenUnited StatesCanadaNetherlandsPortugalRussiaUnited KingdomDenmarkHungarySenegalTanzaniaJapanEstoniaAustraliaPeruPhilippinesThailandLithuaniaPolandGermanyBelgiumBrazilFinlandItalySpainTaiwanSouth Africa
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Frequently asked questions about Cervarix

What is Cervarix used for?

Cervarix is a vaccine developed for the prevention of Human Papillomavirus (HPV) infection, specifically targeting Papillomavirus Type 16/18 Infection. It is used in the context of infectious disease prevention, with clinical trials conducted in healthy male and female subjects aged 9 to 25 years.

Who makes Cervarix?

Cervarix is developed by GSK plc, a biopharmaceutical company listed on the stock exchange under the ticker GSK. The company has conducted extensive clinical research on this vaccine, including multiple Phase 3 trials.

What phase is Cervarix in?

Cervarix is in Phase 3 clinical development. It is an investigational vaccine, meaning it is not yet approved for general use. All 16 clinical trials associated with Cervarix have been completed, with no active trials currently ongoing.

What clinical trials is Cervarix in?

Cervarix has been studied in 16 completed clinical trials, including NCT00309166, NCT00337818, NCT00481767, and NCT00541970. These trials evaluated the vaccine's immunogenicity and safety in healthy subjects, with enrollment ranging from 270 to 961 participants across various countries.

How does Cervarix work?

Cervarix is a vaccine designed to prevent Human Papillomavirus (HPV) infection by targeting Papillomavirus Type 16/18. It works by stimulating the immune system to produce antibodies against these specific HPV types, which are associated with cervical cancer and other HPV-related diseases.

Is Cervarix FDA approved?

Cervarix is an investigational vaccine currently in Phase 3 clinical development. It has not been approved by the FDA, as it remains under clinical investigation. All completed trials have focused on evaluating its immunogenicity and safety profile.