Human Papillomavirus Vaccine Immunogenicity and Safety Trial in Young Adult Women With GSK Biologicals Novel HPV Vaccine

Study Overview
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Brief Summary
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Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Indeed, certain oncogenic types of HPV can infect the cervix (part of the uterus or womb). This infection may go away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. GlaxoSmithKline Biological's has developed a HPV vaccine against the oncogenic types HPV-16 and HPV-18 formulated with the AS04 adjuvant (control vaccine) and is also evaluating novel HPV vaccines formulations. This study will evaluate the long-term immunogenicity and safety of a novel GSK Biological's vaccine in approximately 376 subjects who received the novel vaccine or the control vaccine administered in the primary study. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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A Long-term, Follow-up of the Immunogenicity and Safety of GlaxoSmithKline Biologicals' Novel HPV Vaccine in Healthy Female Subjects Vaccinated in the Primary Study

Conditions
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Infections, Papillomavirus, Papillomavirus Vaccines

Intervention / Treatment
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* Biological: CervarixTM
* Biological: HPV investigational vaccine GSK568893A, different formulations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A female who enrolled in the study 102115 and received three doses of vaccine. Written informed consent obtained from the subject prior to enrolment. Exclusion Criteria: Use (or planned use during the study period) of any investigational or non-registered product or off-label use of licensed product (drug or vaccine). Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling. Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling. Planned administration of any HPV vaccine, other than that foreseen by the study protocol, during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cervarix Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: CervarixTM<br>* Subjects were administered three doses of HPV vaccine<br>|
| Experimental: Cervarix 1 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 1 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|
| Experimental: Cervarix 2 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 2 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|
| Experimental: Cervarix 3 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 3 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|
| Experimental: Cervarix 4 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 4 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|
| Experimental: Cervarix 5 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 5 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|
| Experimental: Cervarix 6 Group<br>Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 6 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: HPV investigational vaccine GSK568893A, different formulations<br>* Subjects were administered three doses of HPV investigational vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) Antibodies. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 8 ELISA units per milliliter (EL.U/mL). | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-16 (HPV-16) Antibodies. | Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 8 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-16 (HPV-16) Antibodies | Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 8 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Number of Seroconverted Subjects Against Human Papillomavirus-18 (HPV-18) Antibodies. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 7 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-18 (HPV-18) Antibodies. | Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 7 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-18 (HPV-18) Antibodies | Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 7 EL.U/mL. | At Months 18, 24, 36 and 48. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against Human Papillomavirus-31 (HPV-31) Antibodies. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 59 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-31 (HPV-31) Antibodies. | Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 59 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Number of Seroconverted Subjects Against Human Papillomavirus-45 (HPV-45) Antibodies. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 59 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Geometric Mean Titers (GMTs) for Human Papillomavirus-45 (HPV-45) Antibodies. | Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 59 EL.U/mL. | At Months 18, 24, 36 and 48. | 
| Number of Subjects With at Least One New Onset of Chronic Disease (NOCDs) | NOCDs include conditions such as diabetes, autoimmune disease, asthma, allergies etc. At least one NOCD = At least one NOCD experienced (regardless of the Medical Dictionary for Regulatory Activities [MedDRA] Preferred Term) | From Month 0 to Months 18, 24, 36 and 48 | 
| Number of Subjects With at Least One Medically Significant Condition (MAEs). | MAEs were defined as adverse events (AEs) prompting emergency room or physician visits that were not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities, and injury. At least one MAE = At least one medically significant AE experienced (regardless of the MedDRA Preferred Term). | From Month 0 to Months 18, 24, 36 and 48 | 
| Number of Subjects With Any 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. Any = Occurrence of any symptom regardless of intensity grade. | From Month 0 to Months 18, 24, 36 and 48 | 
| Number of Subjects With Pregnancy Outcomes. | Pregnancy outcomes were healthy baby, spontaneous abortion and elective abortion. | From Month 0 to Month 18 | 
| Number of Subjects With Pregnancy Outcomes. | Pregnancy outcomes were healthy baby, spontaneous abortion, elective abortion and ongoing pregnancy. | From Month 0 to Month 24 | 
| Number of Subjects With Pregnancy Outcomes. | Pregnancy outcomes were healthy baby, abnormal infant/congenital anomaly, spontaneous abortion and elective abortion. | From Month 0 to Month 36 | 
| Number of Subjects With Pregnancy Outcomes. | Pregnancy outcomes were normal infant, abnormal infant/congenital anomaly, spontaneous abortion and elective termination. | From Month 0 to Month 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV vaccine