Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Vaccine With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and immunogenicity of GSK Biologicals' meningococcal vaccine GSK134612 (MenACWY-TT) co-administered with Cervarix as compared to MenACWY-TT and Cervarix administered alone and the co-administration of MenACWY-TT with Cervarix and Boostrix as compared to MenACWY-TT administered alone and Cervarix co-administered with Boostrix.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine 134612 With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults at 9-25 Years of Age

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612
* Biological: Cervarix®
* Biological: Boostrix®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects and subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. A female between, and including, 9 and 25 years of age at the time of the first vaccination. Written informed consent obtained from parents/guardian of the subject and written informed assent obtained from the subject if the subject is less than legal age, or written informed consent obtained from the subject if the subject has achieved legal age. The legal age will be determined according to local regulations in each participating country. Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will be ≥10 mg/day prednisone or equivalent. Inhaled and topical steroids are allowed. Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after each study dose of vaccine(s), with the exception of licensed inactivated influenza vaccine. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational product or a non-investigational vaccine/product. Previous vaccination with a meningococcal polysaccharide or conjugate vaccine within the last 10 years. History of meningococcal disease since birth. History of serious allergic reaction following any other DTP-containing vaccine or any component of the study vaccines. History of encephalopathy within seven days of administration of a previous pertussis antigen-containing vaccine that is not attributable to another identifiable cause. Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of tetanus-toxoid containing vaccine should not receive Boostrix unless at least 10 years have elapsed since the last dose of tetanus-toxoid containing vaccine. Previous vaccination with a tetanus-toxoid containing vaccine within the previous five years. Temperature of ≥ 40.5°C (105°F) within 48 hours of receipt of a previous dose of DTP vaccine (diphtheria-tetanus-whole cell pertussis [DTPw] and/or diphtheria-tetanus-acellular pertussis [DTaP]), not due to another identifiable cause. Collapse or shock-like state within 48 hours of receipt of a previous dose of DTP vaccine. Seizures with or without fever within three days of a previous dose of DTP vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and history directed physical examination. A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated. History of any allergic disease/reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). Progressive neurologic disorder, unstable neurologic conditions, uncontrolled epilepsy or progressive encephalopathy. History of any neurologic disorders or seizures. A history of ADHD or depression or a history of a single, simple febrile seizure does not exclude a subject. Major congenital defects or serious chronic illness. Previous history of Guillain-Barré Syndrome. Bleeding disorders, such as hemophilia or thrombocytopenia, or subjects on anti-coagulant therapy. Acute disease and/or fever 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. 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 MPL or AS04 adjuvant. History of chronic alcohol consumption and/or drug abuse. Pregnant or lactating female. A subject 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. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.

Ages Eligible for Study
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Minimum Age: 9 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 |
| --- | --- |
| Experimental: Nimenrix+Cervarix (1,2,7-Month) Group<br>Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm.<br>* Other names: Nimenrix®;Biological: Cervarix®<br>* Three doses administered intramuscularly (IM) in the deltoid of the left arm.<br>|
| Experimental: Nimenrix+Cervarix (0,1,6-Month) Group<br>Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm.<br>* Other names: Nimenrix®;Biological: Cervarix®<br>* Three doses administered intramuscularly (IM) in the deltoid of the left arm.<br>|
| Experimental: Cervarix Group<br>Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm. | Biological: Cervarix®<br>* Three doses administered intramuscularly (IM) in the deltoid of the left arm.<br>|
| Experimental: Nimenrix+Cervarix+Boostrix Group<br>Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm.<br>* Other names: Nimenrix®;Biological: Cervarix®<br>* Three doses administered intramuscularly (IM) in the deltoid of the left arm.<br>Biological: Boostrix®<br>* One dose administered intramuscularly (IM) in the deltoid of the left arm.<br>|
| Experimental: Boostrix+Cervarix Group<br>Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm. | Biological: Cervarix®<br>* Three doses administered intramuscularly (IM) in the deltoid of the left arm.<br>Biological: Boostrix®<br>* One dose administered intramuscularly (IM) in the deltoid of the left arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA) | The analysis was performed for the serogroups -MenA, -MenC -MenW-135 and -MenY. Antibody titers, tabulated as geometric mean titers (GMTs), were obtained by serum bactericidal assay using rabbit complement. This analysis was only performed on groups receiving Nimenrix vaccine. | At one month after vaccination with Nimenrix (Month 1) | 
| Anti-HPV-16 and Anti-HPV-18 Concentrations | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). | At one month after vaccination with Cervarix (Month 7) | 
| Number of Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Concentrations Equal to or Above (≥) 1.0 IU/mL | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL). This analysis was only performed on the groups receiving Boostrix vaccine. | At one month after Boostrix vaccination (Month 1) | 
| Anti-Pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations | The antibody concentrations were tabulated as GMCs and expressed as IU/mL. GMCs were only analyzed in subjects receiving Boostrix vaccination. | At one month after Boostrix vaccination (Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titres ≥ 1:8 and ≥ 1:128 | The number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titers ≥ 1:8 and ≥ 1:128 prior to and one month after vaccination with Nimenrix vaccine. | Prior to and one month after vaccination with Nimenrix (Months 0 and 1) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Vaccine Response | rSBA vaccine response for serogroups A, C, W-135 and Y was defined as: For initially seronegative subjects (pre-vaccination titre below the cut-off of 1:8): number of subjects with rSBA antibody titres ≥ 1:32 one month after vaccination. For initially seropositive subjects (pre-vaccination titre ≥ 1:8): number of subjects with rSBA antibody titres at least four times the pre-vaccination antibody titres, one month after vaccination. | At one month after Nimenrix vaccination (Month 1) | 
| Number of Subjects With Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL | The antibody concentrations were tabulated as GMCs and expressed as IU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group. | Prior to and one month after vaccination with Nimenrix (Months 0 and 1) | 
| Anti-T Antibody Concentrations | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). This analysis was only performed for the Nimenrix+Cervarix (1,2,7-Month) Group. | Prior to and one month after vaccination with Nimenrix (Months 0 and 1) | 
| Number of Subjects With Anti-HPV-16 Concentrations ≥ 19 EU/mL and Anti-HPV-18 Concentrations ≥ 18 EU/mL | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL). | Prior to the first dose and one month after the third dose of Cervarix [Month 0 and Month 7/Month 8 in Nimenrix+Cervarix (1,2,7-Month) Group] | 
| Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies | Seroconversion rate is defined as the appearance of antibodies (i.e. titers greater than or equal to the cut-off value) in the serum of subjects who are seronegative before vaccination. The antibody concentrations were calculated as GMCs and expressed as EU/mL. | Prior to and one month after the third dose of Cervarix (Month 0 and Month 7/Month 8) | 
| Anti-HPV-16 and Anti-HPV-18 Concentrations | The antibody concentrations were calculated as GMCs and expressed as EU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group. | Prior to and one month after the third dose of Cervarix (Months 0 and 8) | 
| Booster Responses for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Booster responses to the PT, FHA and PRN antigens were defined as: For initially seronegative subjects (antibody concentrations: < 2.046 IU/ml for anti-FHA, < 2.187 IU/ml for anti-PRN, < 2.693 IU/ml for anti-PT), antibody concentration ≥ 4*cut_off IU/ml at Month 1 post-vaccination; For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration < 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 4 fold the pre-vaccination antibody concentration; For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration ≥ 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 2 fold the pre-vaccination antibody concentration. | At one month after Boostrix vaccination (Month 1) | 
| Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). | Prior to and one month after Boostrix vaccination (Month 0 and Month 1) | 
| Anti-D and Anti-T Antibody Concentrations | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). | Prior to and one month after Boostrix vaccination (Months 0 and 1) | 
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Equal to or Above the Cut-off Value | The antibody concentrations were calculated as GMCs and expressed as IU/mL. Anti-PT assay cut-off=2.693 IU/mL, anti-FHA assay cut-off=2.046 IU/mL, anti-PRN assay cut-off=2.187 IU/mL. | Prior to and one month after Boostrix vaccination (Months 0 and 1) | 
| Number of Subjects Reporting Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Symptoms were presented by vaccination site. Some groups do not have results for Dose 2 because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects Reporting Solicited General Symptoms | Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. Some groups do not have results for Dose 2 because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Unsolicited Adverse Events AE(s) | 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. | During the 31-day (Days 0-30) period following vaccination with Nimenrix, Boostrix or the first dose of Cervarix | 
| Number of Subjects With Serious Adverse Events SAE(s) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (from Month 0 to Month 8) | 
| Number of Subjects With Potential Immune-mediated Diseases (pIMDs) | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | During the entire study period (from Month 0 to Month 8) | 
| Number of Subjects With New Onset Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | During the entire study period (from Month 0 to Month 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diphtheria, Meningococcal vaccines, Immunogenicity, pertussis, Meningococcal meningitis, Meningococcal infections, HPV, Neisseria meningitidis, Vaccines, conjugate, tetanus