Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With GSK Biologicals' Seasonal Influenza Vaccine GSK2321138A in Adults Aged 50 Years and Older

Study Overview
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Brief Summary
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The purpose of this study is to assess immunogenicity, reactogenicity and safety of GSK Biologicals' HZ/su vaccine when its first dose is co-administered with the FLU-D-QIV vaccine in adults aged 50 years or older compared to administration of vaccines separately.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With GSK Biologicals' Seasonal Influenza Vaccine GSK2321138A in Adults Aged 50 Years and Older

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Herpes Zoster vaccine GSK 1437173A
* Biological: GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). A male or female aged 50 years or older, at the time of the first vaccination with the study vaccine(s). Written informed consent obtained from the subject. 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: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent). A prednisone dose of < 20 mg/day is allowed. Inhaled, topical and intra-articular corticosteroids are allowed. Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine(s) (HZ/su and/or FLU-D-QIV vaccines) and ending 30 days after the last dose of HZ/su vaccine. Administration of an influenza vaccine during the six months preceding entry into the study or planned administration up to the last blood sampling with the exception of the FLU-D-QIV vaccine given during this study. Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period. 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 vaccine/product (pharmaceutical product or device). Previous vaccination against VZV or HZ and/or planned administration during the study of a VZV or HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine. History of HZ. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, HIV infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. History of Guillain Barré syndrome. Hypersensitivity to latex. 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, or ≥ 38.0°C /100.4°F on rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. 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. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions before 2 months after the last dose of study vaccine. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study. Any condition which, in the judgment of the investigator would make intramuscular injection unsafe.

Ages Eligible for Study
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Minimum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Co-Ad Group<br>The subjects assigned to the Co-Ad group will receive one injection of the FLU-D-QIV vaccine and one injection of the HZ/su study vaccine during the first visit and a second injection of the HZ/su study vaccine during the third visit, two months later. | Biological: Herpes Zoster vaccine GSK 1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>Biological: GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the dominant arm.<br>* Other names: Fluarix™ Quadrivalent (United States);|
| Active Comparator: Control Group<br>The subjects assigned to the Control group will receive all vaccines separately: one injection of the FLU-D-QIV vaccine at the first visit, one injection of the HZ/su study vaccine at the third visit and a second injection of the HZ/su study vaccine at the fourth visit, all two months apart. | Biological: Herpes Zoster vaccine GSK 1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>Biological: GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the dominant arm.<br>* Other names: Fluarix™ Quadrivalent (United States);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Vaccine Response to Anti-gE Antibodies | The vaccine response(VRR) for anti-gE humoral immunogenicity, as determined by enzyme-linked immunosorbent assay (ELISA),was assessed only in subjects from the GSK1437173A + GSK2321138A Group. The VRR for anti-gE was defined as the percentage of subjects who had at least: a 4-fold increase in the post-dose 2 anti-gE antibody concentration as compared to the pre-vaccination anti-gE antibody concentration, for subjects who were seropositive at baseline (cut-off ≥ 97 mIU/ml), or, a 4-fold increase in the post dose 2 anti-gE antibody concentrations as compared to the anti-gE antibodies cut-off value for seropositivity, for subjects who were seronegative at baseline (cut-off < 97 mIU/ml). | At one month post-dose 2 (Month 3) | 
| Vaccine Response for Anti-gE Humoral Immunogenicity | The vaccine response(VRR) for anti-gE humoral immunogenicity, as determined by enzyme-linked immunosorbent assay (ELISA),was assessed only in subjects from the GSK1437173A + GSK2321138A Group. The VRR for anti-gE was defined as the percentage of subjects who had at least: a 4-fold increase in the post-dose 2 anti-gE antibody concentration as compared to the pre-vaccination anti-gE antibody concentration, for subjects who were seropositive at baseline (cut-off ≥ 97 mIU/ml), or, a 4-fold increase in the post dose 2 anti-gE antibody concentrations as compared to the anti-gE antibodies cut-off value for seropositivity, for subjects who were seronegative at baseline (cut-off < 97 mIU/ml).Criterion used: the objective was met if the Lower Limit (LL) of the 95% confidence interval (CI) of the VRR for anti-gE antibody concentrations was at least 60%. | At one month post-dose 2 (Month 3) | 
| Adjusted Geometric Mean ELISA Concentrations of Anti-gE Antibodies | Geometric means (GMs) of post-vaccination concentrations (Month 3 for GSK1437173A + GSK2321138A group and Month 5 for Control group) was calculated conditionally to the means of the pre-vaccination log-transformed concentrations for anti-gE (Month 0 for GSK1437173A + GSK2321138A group and Month 2 for Control group). Adjusted Least Squares (LS) means and difference of LS means between the groups were calculated together with 2-sided 95% CIs and back-transformed to the original units to provide GMCs. | At one month post-dose 2 (Month 3 for GSK1437173A + GSK2321138A group and Month 5 for Control group) | 
| FLU Haemagglutination Inhibition (HI) Antibody Titers | For each strain included in the FLU-D-QIV vaccine, an ANOVA model was used to analyze post-vaccination log-transformed titers. The fixed-effect model included the minimization variable (age cohorts) and the treatment as fixed effect. The pre-vaccination log-transformed concentrations were included as continuous covariate. Geometric Means (GM) of post-vaccination titers (Day 21) were calculated conditionally to the means of the pre-vaccination log-transformed titers (Month 0) for each strain. Adjusted GMTs (GMTs adjusted for baseline titers) and Adjusted GMT ratios were calculated together with 2-sided 95% CIs. | At Day 21 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With FLU HI Antibody Titers ≥1:10 | FLU HI antibodies were assessed in four strains: Flu A/California/7/2009 H1N1, Flu A/Texas/50/2012 H3N2, Flu B/Brisbane/60/2008 Victoria and Flu B/Massachusetts (Massach)/2/2012 Yamagata (Yama). Cut-off titer for seropositivity was 1:10. | At Day 0 (PRE) and 21 post vaccination | 
| Number of Seroprotected Subjects With HI Antibody Titers ≥ 1:40 | Seroprotection rate is defined as the percentage of vaccines with a serum HI titer ≥1:40 that usually was accepted as indicating protection. FLU HI antibodies were assessed in four strains: Flu A/California/7/2009 H1N1, Flu A/Texas/50/2012 H3N2, Flu B/Brisbane/60/2008 Victoria (Vic) and Flu B/Massachusetts(Massach)/2/2012 Yamagata (Yama). | At Day 0 (PRE) and at Day 21 post vaccination | 
| FLU Haemagglutination Inhibition (HI) Antibody Titers | HI antibody titres against the four influenza vaccine strains Flu A/California/7/2009, Flu A/Texas/50/2012, Flu B/Brisbane/60/2008 Victoria (Vic) and Flu B/Massachusetts (Massach)/2/2012 Yamagata (Yamma) were expressed as geometric mean titers (GMTs). | At Day 0 (PRE) and Day 21 post vaccination | 
| Number of Seroconverted Subjects in Terms of HI Antibodies | The number of seroconverted subjects was assessed in terms of HI antibodies against the four influenza vaccine strains Flu A/California/7/2009, Flu A/Texas/50/2012, Flu B/Brisbane/60/2008 Victoria and Flu B/Massachusetts/2/2012 Yamagata. | At Day 21 post vaccination | 
| Geometric Mean Ratio for Flu HI Antibodies Post-vaccination Titer | The geometric mean ratio for Flu HI antibodies against the four influenza vaccine strains Flu A/California/7/2009, Flu A/Texas/50/2012, Flu B/Brisbane/60/2008 Victoria and Flu B/Massachusetts/2/2012 Yamagata was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. | At Day 21 post vaccination | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 (G3) pain = pain that prevented normal activity. Grade 3 (G3) redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Relationship analysis was not performed. | Within 7 days (Days 0-6) after each vaccine dose | 
| Number of Subjects With 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 100 millimeters (mm) of injection site. Relationship analysis was not performed. | Within 7 days (Days 0-6) across doses | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 7 days (Days 0-6) after each vaccine dose | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 7 days (Days 0-6) across doses | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | 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 30 days (Days 0-29) after vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | From first vaccination up to Month 18 (study end) | 
| 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. | From first vaccination up to Month 18 (study end) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, co-administration, Herpes zoster, FLU-D-QIV, Adults, Safety