Study to Evaluate Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A When Co-administered With Pneumovax 23™ 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 the immunogenicity, reactogenicity and safety of the GSK Biologicals HZ/su candidate vaccine when its first dose is co-administered with Pneumovax 23™ vaccine in adults aged 50 years or older.The impact of HZ/su vaccine on Pneumovax 23™ vaccine immune response will also be evaluated.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With Pneumovax 23™ in Adults Aged 50 Years and Older

Conditions
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Herpes Zoster, Herpes Zoster Vaccine

Intervention / Treatment
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* Biological: Herpes Zoster vaccine GSK 1437173A
* Biological: Licensed pneumococcal polysaccharide conjugate vaccine (23-valent, adsorbed), Pneumovax 23™


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. 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 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. 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) and ending 30 days after the last dose of study vaccine. This includes any type of vaccine such as live, inactivated and subunit vaccines. Administration of long-acting immune-modifying drugs 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. Previous vaccination against Varicella-zoster virus (VZV) or HZ and/or planned administration during the study of an HZ or VZV vaccine other than the study vaccine. History of HZ. History of documented pneumococcal infection within 5 previous years. Prior receipt of any pneumococcal vaccine or planned use of this vaccine during the study period, other than the study vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy . History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C /99.5°F by oral route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhea, 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 persons with cerebrospinal fluid (CSF) leaks, cochlear implants, chronic renal failure, nephrotic syndrome, and functional or anatomic asplenia. 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 (IM) 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>Subjects received one dose of the GSK1437173A study vaccine and one dose of the Pneumovax™ 23 vaccine at Day 0 and a second dose of GSK1437173A study vaccine at Month 2. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax™ 23 was administered intramuscularly, in the deltoid region of the dominant arm. | Biological: Herpes Zoster vaccine GSK 1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>Biological: Licensed pneumococcal polysaccharide conjugate vaccine (23-valent, adsorbed), Pneumovax 23™<br>* One dose administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>* Other names: Pneumo 23™;|
| Active Comparator: Control Group<br>Subjects received one dose of the Pneumovax™ 23 vaccine at Day 0, one dose of the GSK1437173A study vaccine at Month 2 and a second dose of the GSK1437173A study vaccine at Month 4. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax™ 23 was administered intramuscularly, in the deltoid region of the dominant arm. | Biological: Herpes Zoster vaccine GSK 1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>Biological: Licensed pneumococcal polysaccharide conjugate vaccine (23-valent, adsorbed), Pneumovax 23™<br>* One dose administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>* Other names: Pneumo 23™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Vaccine Response for Anti-gE Antibodies | Vaccine response rate for anti-gE antibody concentrations, as determined by enzyme-linked immunosorbent assay (ELISA), in subjects from the Co-Ad group. Vaccine response defined as : For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL) For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration | At Month 3 | 
| Anti-glicoprotein E (gE) Antibody Concentrations | Antibody concentrations were determined by ELISA, presented as geometric mean concentrations and expressed as milli international units per milliliter (mIU/mL). | At one month post-dose 2 (Month 3 for the Co-Ad Group and Month 5 for the Control Group) | 
| Anti-pneumococcal Antibody Titers | Anti-pneumococcal antibody titers were presented as geometric mean titers (GMTs) for the 12 following serotypes as determined by Opsonophagocytic Assay (OPA): 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. | At one month post-dose (Month 1) | 
| Adjusted Ratios of Geometric Mean Titers (GMTs) Between Groups | The Adjusted ratios of GMTs between groups (Control group and Co-Ad group) were presented for each individual pneumococcal conjugate serotype Opsonophagocytic Activity (OPA). | At 1 month after vaccination | 
| Adjusted GMCs Between Groups | The Adjusted ratios of GMCs between groups (Control group and Co-Ad group) was presented for anti-gE antibody ELISA concentrations | At 1 month after last vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms, by Dose | 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. The Co-Ad Group received only 2 vaccine doses. | Within 7 days (Days 0 - 6) after each vaccination | 
| Number of Subjects With Solicited Local Symptoms, Across Doses, by Vaccine | 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. | Within 7 days (Days 0 - 6) after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. 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. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Days With Any Solicited Local and General Symptoms | The Co-Ad Group received only 2 vaccine doses, hence the number of participants for the Dose 3 categories in this group is 0. | Within 7 days (Days 0 - 6) after each vaccination | 
| 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. | From the first dose up to 30 days post last vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) [From the First Dose up to 30 Days Post Last Vaccination Period] | 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 the first dose up to 30 days post last vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) [From 30 Days Post Last Vaccination up to Study End] | 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 30 days post last vaccination up to study end | 
| Number of Subjects With Potential Immune Mediated Diseases (pIMDs) [From First Vaccination up to 30 Days Post Last Vaccination] | Potential immune-mediated diseases (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 30 days post last vaccination (Month 0 - Month 3 for the Co-Ad Group & Month 0 - Month 5 for the Control Group) | 
| Number of Subjects With Potential Immune Mediated Diseases (pIMDs) [During the Period Starting After 30 Days Post Last Vaccination up to Study End] | Potential immune-mediated diseases (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 period starting after 30 days post last vaccination up to study end (Month 3 - Month 14 for the Co-Ad Group & Month 5 - Month 16 for the Control Group) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumovax 23, Co-administration, Herpes zoster, Immunogenicity, Safety, Adults