Evaluation of Safety and Immunogenicity of Co-administering HPV Vaccine With Other Vaccines in Healthy Female Subjects

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. Vaccination of pre-teens and adolescents, ideally before sexual debut and thus before exposure to oncogenic HPV, is a rational strategy for prevention of cervical cancer, and so HPV vaccination could complement the existing pre-adolescent/adolescents platform. Therefore, this Phase 3b study is designed to evaluate the safety and immunogenicity of co-administering Boostrix and/or Menactra with GSK Biologicals' HPV vaccine (580299) as compared to the administration of any of the vaccines alone. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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A Randomized, Open Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine Co-administered Intramuscularly With Boostrix® and/or Menactra™ in Healthy Female Subjects Aged 11-18 Years

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
* Biological: Menactra TM
* Biological: Boostrix TM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can, and will, comply with the requirements of the protocol should be enrolled in the study. A female between, and including, 11 and 18 years of age at the time of the first vaccination. Written informed consent obtained from parents/legally acceptable representative of the subject and written informed assent obtained from the subject if the subject is less than 18 years of age, or written informed consent obtained from the subject if the subject is 18 years of age. Healthy subjects, as established by medical history and history-directed physical examination, before entering into the study. Previously completed routine childhood vaccinations against diphtheria, tetanus and pertussis diseases, according to the recommended vaccination schedule at the time. Subjects must have a negative urine pregnancy test. Subjects of childbearing potential at the time of study entry are required to be abstinent or use adequate contraceptive precautions for 30 days prior to vaccination. Subjects also are required to agree to continue such precautions for two months after completion of the vaccination series. Female subjects who reach menarche (began menstruating) during the study and therefore become of child-bearing potential are required to agree to follow the same precautions. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Concurrently participating in another clinical study, at any time during the study period (up to the Month 12/13 visit), in which the subject has been or will be exposed to an investigational or a non-investigational product. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after each dose of vaccine. Administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window. A woman planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose. Pregnant or breastfeeding women. Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period. previous administration of components of the investigational vaccine Administration of a pre-school booster of diphtheria, tetanus, pertussis vaccine within the previous five years. Administration of a diphtheria-tetanus booster or tetanus-diphteria-acellular pertussis (Tdap) vaccine within the previous five years. Previous vaccination against Neisseria meningitidis. Hypersensitivity to latex. Cancer or autoimmune disease under treatment. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine. History of encephalopathy within seven days of administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause. Progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy. Temperature of >= 105°F within 48 hours of receipt of a prior dose of diphteria- tetanu-pertussis (DTP) vaccine, not due to another identifiable cause. Collapse or shock-like state within 48 hours of receipt of a prior dose of DTP vaccine. Seizures with or without fever within three days of a prior dose of DTP vaccine. Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid within the previous 10 years. Previous history of Guillain-Barré syndrome. Any confirmed or suspected immunosuppressive or immunodeficient condition Acute disease at the time of enrolment. All vaccines can be administered to persons with a minor illness Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 18 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 |
| --- | --- |
| Experimental: Cervarix + Boostrix/Menactra Group<br>Subjects received Cervarix and Boostrix at Month 0, Menactra and Cervarix at Month 1 and Cervarix alone at Month 6. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>Biological: Menactra TM<br>* One dose of vaccine administered intramuscularly<br>Biological: Boostrix TM<br>* One dose of vaccine administered intramuscularly<br>|
| Experimental: Cervarix + Menactra/Boostrix Group<br>Subjects received Menactra and Cervarix at Month 0, Boostrix and Cervarix at Month 1 and Cervarix alone at Month 6. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>Biological: Menactra TM<br>* One dose of vaccine administered intramuscularly<br>Biological: Boostrix TM<br>* One dose of vaccine administered intramuscularly<br>|
| Experimental: Cervarix + Boostrix + Menactra Group<br>Subjects received Boostrix, Menactra and Cervarix at Month 0 and Cervarix alone at Months 1 and 6. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>Biological: Menactra TM<br>* One dose of vaccine administered intramuscularly<br>Biological: Boostrix TM<br>* One dose of vaccine administered intramuscularly<br>|
| Experimental: Boostrix/Cervarix Group<br>Subjects received Boostrix at Month 0 and Cervarix at Months 1, 2 and 7. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>Biological: Menactra TM<br>* One dose of vaccine administered intramuscularly<br>Biological: Boostrix TM<br>* One dose of vaccine administered intramuscularly<br>|
| Experimental: Menactra/Cervarix Group<br>Subjects received Menactra at Month 0 and Cervarix at Months 1, 2 and 7. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>Biological: Menactra TM<br>* One dose of vaccine administered intramuscularly<br>|
| Experimental: Cervarix Group<br>Subjects received Cervarix at Months 0, 1 and 6. | Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)<br>* Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibody Concentrations Above 1.0 International Unit Per Milliliter (IU/mL) | Anti-D and anti-T antibodies cut-off values assessed include 1.0 international unit per milliliter (IU/mL) | Before and one month after vaccination with Boostrix | 
| Concentration of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Concentrations given as Geometric Means Concentrations (GMCs) | Before and one month after vaccination with Boostrix | 
| Titer of Meningococcal Serogroup A (Anti-A), Meningococcal Serogroup C (Anti-C), Meningococcal Serogroup Y (Anti-Y) and Meningococcal Serogroup W-135 (Anti-W135) Antibodies | Titers given as Geometric Mean Titers (GMTs) | Before and one month after vaccination with Menactra | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-human Papilloma Virus 16 (Anti-HPV16) and Anti-human Papilloma Virus 18 (Anti-HPV18) Antibody Concentrations Above Pre-defined Cut-off Values | Cut-off values assessed include 8 enzyme-linked immunosorbent assay units Per Milliliter (EL.U/mL) for anti-HPV16 antibodies and 7 EL.U/mL for anti-HPV18 antibodies. | Before vaccination (PRE), one month post Dose 2 (Mth2) and one and six months post Dose 3 (Mth 7 and Mth 12) | 
| Number of Subjects With Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibody Concentrations Above 0.1 International Unit Per Milliliter (IU/mL) | Anti-D and anti-T antibodies cut-off values assessed include 0.1 international unit per milliliter (IU/mL) | Before and one month after vaccination with Boostrix | 
| Concentration of Anti-D and Anti-T Antibodies | Concentrations given as Geometric Mean Concentrations (GMCs) | Before and one month after vaccination with Boostrix | 
| Number of Subjects With Booster Response for Anti-D and Anti-T | Booster responses for anti-D and anti-T defined as: For initially seronegative subjects (pre-vaccination titer below cut-off: < 0.1 IU/mL): antibody titer at least 4 times the cut-off (post-vaccination titer ≥ 0.4 IU/mL) For initially seropositive subjects (pre-vaccination titer above 0.1 IU/mL): an increase in antibody titer of at least 4 times the pre-vaccination titer | One month after vaccination with Boostrix | 
| Number of Subjects With Booster Response for Anti-PT, Anti-FHA and Anti-PRN | Booster responses defined as: For initially seronegative subjects (pre-vaccination titer below cut-off: < 5 EL.U/mL): antibody titers at least 4 times the cut-off, For initially seropositive subjects with pre-vaccination titer above 5 EL.U/mL and < 20 EL.U/mL: an increase in antibody titers of at least 4 times the pre-vaccination titer, For initially seropositive subjects with pre-vaccination titer ≥ 20 EL.U/mL: an increase in antibody titers of at least two times the pre-vaccination titer | One month after vaccination with Boostrix | 
| Number of Subjects With Anti-A, Anti-C, Anti-Y and Anti-W135 Vaccine Response | Vaccine responses for anti-A, C, Y and W-135 defined as: For initially seronegative subjects (pre-vaccination titer below cut-off of 8): antibody titers at least 4 times the cut-off (post vaccination titer ≥ 32) For initially seropositive subjects (pre-vaccination titer above 8): antibody titers at least 4 times the pre-vaccination antibody titer | One month after vaccination with Menactra | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | During the 7-day period following each vaccination | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include Arthralgia, fatigue, fever, gastrointestinal, headache, myalgia, rash and urticaria | During the 7-day period following each vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. | During the 30-day period following each vaccination | 
| Number of Subjects Reporting Serious Adverse Events | Serious adverse events assessed include medical occurrences that results in death, is 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. | During the active phase of the study (up to Month 7 or Month 8) and throughout the entire study (up to Month 12 or Month 13) | 
| Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes | During the active phase of the study (up to Month 7 or Month 8) and throughout the entire study period (up to Month 12 or Month 13) | 
| Number of Subjects Reporting Medically Significant Adverse Events (AEs) | Medically significant AEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or SAEs that are not related to common diseases. | During the active phase (up to Month 7 or Month 8) and throughout the entire study (up to Month 12 or Month 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, HPV, diptheria, pertussis, tetanus, meningitis