Evaluation of Immunogenicity and Safety of Human Papillomavirus (HPV) Vaccine Co-administered With Another Vaccine 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 necessary 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. Thus, HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. This Phase IIIb study is designed to evaluate the immunogenicity and safety of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 VLP AS04 (Cervarix TM) vaccine as compared to the administration of either vaccine alone.

Official Title
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Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV Vaccine (580299) Co-administrated With a Commercially Available Vaccine in Healthy Female Adolescents

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: HPV Vaccine (GSK580299) Cervarix TM
* Biological: Engerix B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they and/or their parents/legally acceptable representatives (LARs) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study. A female between, and including, 9 and 15 years of age (has not attained her 16th birthday) at the time of the first vaccination. Written informed consent obtained from the subject's parent/LAR prior to the enrolment. In addition, written informed assent must be obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Subjects must not be pregnant. Absence of pregnancy should be verified with a urine pregnancy test. If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche (begin menstruating) during the study, and therefore become of childbearing potential, must agree to follow the same precautions. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12). 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 such as meningococcal, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed. Concurrently participating in another clinical study, at any time during the study period (up to the Month 12 telephone contact), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) 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. Previous vaccination against hepatitis B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period. History of hepatitis B infection. Known exposure to hepatitis B within the previous 6 weeks. Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests. Cancer or autoimmune disease under treatment. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three 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: 9 Years
Maximum Age: 15 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 & Engerix Group<br>Subjects received 3 doses of Cervarix™ (Human Papillomavirus [HPV] vaccine) co-administered with Engerix™ (Hepatitis B [HBV] vaccine) according to a 0, 1, 6-month schedule. | Biological: HPV Vaccine (GSK580299) Cervarix TM<br>* IM administration<br>Biological: Engerix B<br>* IM administration<br>|
| Experimental: Cervarix Group<br>Subjects received 3 doses of Cervarix™ (Human Papillomavirus [HPV] vaccine) according to a 0, 1, 6-month schedule. | Biological: HPV Vaccine (GSK580299) Cervarix TM<br>* IM administration<br>|
| Active Comparator: Engerix Group<br>Subjects received 3 doses of Engerix™ (Hepatitis B [HBV] vaccine) according to a 0, 1, 6-month schedule. | Biological: Engerix B<br>* IM administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection | Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination. Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL. | Month 7 | 
| Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Concentrations Above the Cut-off Value for Seroconversion | Only groups which had received the HPV vaccine were included in the analysis. Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL. Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination. | Month 7 | 
| Anti-HPV-16/18 Antibody Titres | Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs). Only groups which had received the HPV vaccine were included in the analysis. Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination. | Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Value for Seroconversion | Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination. Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL. | Month 7 | 
| Anti-HBs Antibody Titres | Antibody titers for anti-HBs are given as Geometric Mean Titers (GMTs) in mIU/mL. Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination. | Month 7 | 
| Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above the Cut-off Value for Seroconversion | Only groups which had received the HPV vaccine were included in the analysis. Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL. Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination. | Month 2 | 
| Anti-HPV-16/18 Antibody Titres | Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs). Only groups which had received the HPV vaccine were included in the analysis. Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination. | Month 2 | 
| Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroconversion | Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination. Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL. | Month 2 | 
| Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection | Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination vaccination. Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL. | Month 2 | 
| Anti-HBs Antibody Titers | Anti-HBs antibody titers are given as GMTs in mIU/mL. Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination. | Month 2 | 
| Number of Subjects Reporting Any Solicited Local Symptoms | Solicited local symptoms included injection site pain, redness and swelling. Any solicited local symptom is occurence of a symptom regardless of its intensity. | During the 7-day period (Days 0 - 6) following vaccination | 
| Number of Subjects Reporting Grade 3 Solicited Local Symptoms | Solicited local symptoms include injection site pain, redness and swelling. Grade 3 pain is pain that prevented normal everyday activities. Grade 3 redness is redness that was > 50 mm. Grade 3 swelling is swelling that was > 50 mm. | During the 7-day period (Days 0-6) following vaccination | 
| Number of Subjects Reporting Any Solicited General Symptoms | Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria. Any solicited general symptom is the occurence of the symptom regardless of its intensity or relationship to study vaccination. | During the 7-day (Days 0-6) period following vaccination. | 
| Number of Subjects Reporting Grade 3 Solicited General Symptoms | Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria. Grade 3 arthralgia, fatigue, gastrointestinal, headache, myalgia and rash were symptoms that prevented normal activity. Grade 3 temperature was temperature > 39 degrees Celsius. Grade 3 urticaria was urticaria distributed on at least 4 body areas. | During the 7-day (Days 0-6) period following vaccination | 
| Number of Subjects Reporting Related Solicited General Symptoms | Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria. Related solicited general symptoms were those symptoms assessed by the investigators as related to the study vaccination. | During the 7-day period (Days 0 - 6) following vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination 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 was an AE that prevented normal activities. Related AE was an AE that was assessed by the investigator as related to the study vaccination. | During the 30-day period (Days 0 - 29) following any vaccination | 
| Number of Subjects Reporting Any and Causally Related to Vaccination 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 SAEs were SAEs assessed by the investigators as related to the vaccination. * Grade 3 SAEs were not assessed. | Throughout the active phase of the study (up to Month 7). | 
| Number of Subjects Reporting Any and Causally Related to Vaccination 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. * Grade 3 SAEs were not assessed. | Throughout the safety follow-up (month 7 up to Month 12). | 
| Number of Subjects Reporting Medically Significant Conditions | Medically significant conditions (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases). | Throughout the active phase of the study (up to Month 7) | 
| Number of Subjects Reporting Medically Significant Conditions | Medically significant conditions (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases). | Throughout the safety follow-up (month 7 up to Month 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Co-administration, HPV vaccine, Cervical cancer