Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Conjugate Vaccine (GSK134612) When Co-administered With Boostrix® in Subjects Between 11 and 25 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the meningococcal conjugate vaccine (MenACWY-TT) co-administered with Boostrix® versus each of the two vaccines given separately in healthy adolescents and young adults.

Official Title
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Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Meningococcal Conjugate Vaccine (GSK134612) When Co-administered With Boostrix® in Healthy Adolescents and Young Adults Between 11 and 25 Years of Age

Conditions
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Infections, Meningococcal

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects as established by medical history and clinical examination before entering into the study. 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 male or female between, and including, 11 and 25 years of age at the time of the first vaccination. Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject. Written informed assent obtained from the subjects when applicable according to local regulations. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy. 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 two months after completion of the vaccination series. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccines 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 mean prednisone ≥ 10 mg/day, or equivalent. Inhaled and topical steroids are allowed. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of vaccine and ending 30 days after the last dose of vaccine, 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 or a non-investigational product. Previous vaccination with a meningococcal vaccine. History of meningococcal disease. Vaccination with a DTP-containing vaccine within the previous five years. History of serious allergic reaction following any other DTP-containing vaccine or any component of the study vaccines. History of encephalopathy within seven days following administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause. Temperature of ≥ 40.5°C (105°F) within 48 hours of receipt of a previous dose of DTP vaccine, 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. Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid (TT) within the previous ten years. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination during the study period. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). Progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy. History of any neurologic disorders or seizures, including Guillain-Barré syndrome (GBS). History of a simple, single febrile seizure is permitted. Bleeding disorders, such as haemophilia or thrombocytopenia, or subjects on anticoagulant therapy. 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. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimenrix+ Boostrix Group<br>Healthy male or female subjects, between and including 11 and 25 years of age, who received one dose of Nimenrix vaccine co-administered with one dose of Boostrix vaccine, at Month 0, administered by intramuscular injection into the deltoid muscle. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid muscle of the arm.<br>* Other names: Nimenrix;Biological: Boostrix®<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm (in Co-ad Group) and left arm (in TdapACWY and ACWYTdap Groups).<br>* Other names: Tdap;|
| Experimental: Nimenrix Group<br>Healthy male or female subjects, between and including 11 and 25 years of age, who received one dose of Nimenrix vaccine at Month 0 and one dose of Boostrix vaccine at Month 1. Both vaccines were administered by intramuscular injection into the deltoid muscle. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid muscle of the arm.<br>* Other names: Nimenrix;Biological: Boostrix®<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm (in Co-ad Group) and left arm (in TdapACWY and ACWYTdap Groups).<br>* Other names: Tdap;|
| Experimental: Boostrix Group<br>Healthy male or female subjects, between and including 11 and 25 years of age, who received one dose of Boostrix vaccine at Month 0 and one dose of Nimenrix vaccine at Month 1. Both vaccines were administered by intramuscular injection into the deltoid muscle. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid muscle of the arm.<br>* Other names: Nimenrix;Biological: Boostrix®<br>* One dose administered intramuscularly (IM) in the deltoid of the right arm (in Co-ad Group) and left arm (in TdapACWY and ACWYTdap Groups).<br>* Other names: Tdap;|

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 and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). The primary outcome results only refer to Nimenrix+Boostrix Group and Nimenrix Group. | One month after Nimenrix vaccination (i.e. Month 1 for Nimenrix+Boostrix and Nimenrix Groups and Month 2 for Boostrix Group) | 
| Number of Subjects With Anti-D and Anti-T Concentrations Above the Cut-off Value | The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). The reference cut-off value was an antibody concentration ≥ 1 IU/mL. The primary outcome results only refer to Nimenrix+Boostrix Group and Boostrix Group. | One month after Boostrix vaccination (i.e. 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 adjusted geometric mean concentrations (GMCs) and expressed as international units per millilitre (IU/mL). The primary outcome results only refer to Nimenrix+Boostrix Group and Boostrix Group | One month after Boostrix vaccination (i.e. 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 Above the Cut-off Values | The reference cut-off values of the assay were rSBA-Men antibody concentrations ≥ 1:128 and ≥ 1:8. | Prior to (i.e. Month 0 for Nimenrix+Boostrix and Nimenrix Groups and Month 1 for Boostrix Group) and one month after Nimenrix vaccination (i.e. Month 1 for Nimenrix+Boostrix and Nimenrix Groups and Month 2 for Boostrix Group) | 
| Vaccine Response for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibodies | rSBA vaccine response for serogroups A, C, W-135 and Y was defined as: For initially seronegative subjects (pre-vaccination titer below the cut-off of 1:8): number of subjects with rSBA antibody titers ≥ 1:32 one month after vaccination. For initially seropositive subjects (pre-vaccination titer ≥ 1:8): number of subjects with rSBA antibody titers at least four times the pre-vaccination antibody titers, one month after vaccination. | One month after Nimenrix vaccination (i.e. Month 1 for Nimenrix+Boostrix and Nimenrix Groups and Month 2 for Boostrix Group) | 
| Anti-D Antibody Concentrations | The antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). | Prior to (PRE i.e. Month 0 for Nimenrix + Boostrix Group and Boostrix Group and Month 1 for Nimenrix Group) and one month after Boostrix vaccination (POST i.e. Month 1 for Nimenrix + Boostrix Group and Boostrix Group and Month 2 for Nimenrix Group) | 
| Anti-T Antibody Concentrations | The antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). | Prior to (i.e. Month 0 for Nimenrix + Boostrix Group and Boostrix Group and Month 1 for Nimenrix Group), one month after Nimenrix vaccination and one month after Boostrix vaccination | 
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above the Cut-off Value | The reference cut-off value of the assay was an antibody concentration ≥ 5.0 ELISA units per milliliter (EL.U/mL) | Prior to (i.e. Month 0 for Nimenrix + Boostrix Group and Boostrix Group and Month 1 for Nimenrix Group) and one month after Boostrix vaccination (i.e. Month 1 for Nimenrix + Boostrix Group and Boostrix Group and Month 2 for Nimenrix Group) | 
| Booster Responses for Anti-PT, Anti-FHA and Anti-PRN Concentrations | Booster response to the pertussis components is defined as: For initially seronegative subjects, antibody concentration ≥ 4*cut_off (IU/mL) at one month post-vaccination; For initially seropositive subjects with pre-vaccination antibody concentration < 4*cut_off (IU/mL) : antibody concentration at one month post-vaccination ≥ 4 fold the pre-vaccination antibody concentration; For initially seropositive subjects with pre-vaccination antibody concentration ≥ 4*cut_off (IU/mL) : antibody concentration at one month post-vaccination ≥ 2 fold the pre-vaccination antibody concentration. | One month after Boostrix vaccination (i.e. Month 1 for Nimenrix + Boostrix Group and Boostrix Group and Month 2 for Nimenrix Group) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Results are presented across doses, after each vaccination (with Nimenrix, Boostrix, total). | During the 4-day (Days 0-3) following each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. 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. Results are presented across doses. | During the 4-day (Days 0-3) period following each vaccination | 
| Number of Subjects With New Onset of Chronic Diseases (NOCDs) | NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. | Throughout the study (Month 0 up to Month 2) | 
| 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) post-vaccination period | 
| Number of Subjects With Serious Adverse Events SAE(s) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | Throughout the study (Month 0 up to Month 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Young adults, Adolescents, Reactogenicity, Diphtheria, pertussis, Immunogenicity, Tetanus, Meningococcal vaccines, Safety, Neisseria meningitidis, Healthy