Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With Prevenar13 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 and safety of GSK Biologicals' HZ vaccine when its first dose is co-administered with a pneumococcal polysaccharide conjugate vaccine (Prevenar13) in adults aged ≥50 YOA, as compared to the control group where the two HZ/su doses are administered subsequent to Prevenar13.

Detailed Description
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Following the initial approval of the GlaxoSmithKline (GSK) Biologicals' HZ/su vaccine, the protocol was amended to indicate that the trademark is Shingrix. In addition, the term candidate vaccine has been replaced by study vaccine throughout the protocol.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With Prevenar13 in Adults Aged 50 Years and Older

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: HZ/su vaccine GSK1437173A
* Biological: Prevenar13


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. Written informed consent obtained from the subject prior to performance of any study specific procedure. A male or female, aged ≥50 YOA at the time of the first vaccination with the study vaccine(s). Female subjects of non-childbearing potential may be enrolled in the study. 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 during the period starting 30 days before the first dose of study vaccines (Day -30 to Day 1), or planned use during the study period. Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe. Use or anticipated use of immunosuppressants or other immune-modifying drugs during the period starting six months prior to study start and during the whole study period. This includes chronic administration of corticosteroids (>14 consecutive days of prednisone at a dose of ≥20 mg/day [or equivalent]), long-acting immune modifying agents or immunosuppressive/cytotoxic therapy. Inhaled, topical and intra-articular corticosteroids are allowed. Administration or planned administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration. This includes any type of vaccine such as (but not limited to) live, inactivated and subunit vaccines. 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 and/or planned administration of an HZ or VZV vaccine other than the study vaccine during the study period. History of HZ. History of documented pneumococcal infection within 5 previous years. Prior receipt of any pneumococcal vaccine or planned use during the study period, other than the study vaccines. 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 enrollment. Fever is defined as temperature ≥ 38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity. Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products during the period starting 3 months before 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 person with cerebrospinal fluid (CSF) leaks, cochlear implants, chronic renal failure, nephrotic syndrome and functional or anatomic asplenia. Any medical condition that in the judgment of the investigator would prevent the subject from participating in the study.

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>Adults aged ≥50 years of age who received the first dose of GSK1437173A and one dose of Prevenar13 at Day 1 and the second dose of GSK1437173A at Month 2. Both vaccines were administered intramuscularly, GSK1437173A was administered in the deltoid muscle of the non-dominant arm, while Prevenar13 was administered in the deltoid muscle of the dominant arm | Biological: HZ/su vaccine GSK1437173A<br>* 2 doses of 0.5 mL of the vaccine in a 0,2 Months schedule. Administered by intramuscular injection into the deltoid muscle of the non-dominant arm.<br>Biological: Prevenar13<br>* 1 dose of 0.5 mL of the vaccine. Administered by intramuscular injection into the deltoid muscle of the dominant arm.<br>* Other names: PCV13;|
| Active Comparator: Control Group<br>Adults aged ≥50 years of age who received one dose of Prevenar13 at Day 1, the first dose of GSK1437173A at Month 2 and the second dose of GSK1437173A at Month 4. Both vaccines were administered intramuscularly, GSK1437173A was administered in the deltoid muscle of the non-dominant arm, while Prevenar13 was administered in the deltoid muscle of the dominant arm | Biological: HZ/su vaccine GSK1437173A<br>* 2 doses of 0.5 mL of the vaccine in a 0,2 Months schedule. Administered by intramuscular injection into the deltoid muscle of the non-dominant arm.<br>Biological: Prevenar13<br>* 1 dose of 0.5 mL of the vaccine. Administered by intramuscular injection into the deltoid muscle of the dominant arm.<br>* Other names: PCV13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Vaccine Response for Anti-glycoprotein E (Anti-gE) in Co-Ad Group | Vaccine response rate (VRR) for Varicella Zoster Virus (VZV) anti-glycoprotein E (gE) humoral immunogenicity was determined by Enzyme Limked Immunosorbent Assay (ELISA). The VRR for anti-gE is defined as the percentage of subjects who had at least: a 4-fold increase in the anti-gE antibodies concentration as compared to the pre-vaccination anti-gE antibodies concentration, for subjects who are seropositive at baseline, or, a 4-fold increase in the anti-gE antibodies concentration as compared to the anti-gE antibodies cut-off value for seropositivity, for subjects who are seronegative at baseline. | One month post-dose 2 (Month 3) | 
| Anti-gE Antibody Concentrations | Anti-gE antibody concentrations in terms of Geometric Mean concentrations (GMC) were determined by ELISA and expressed as milli-international units per milliliter (mIU/mL) | One month post-dose 2 (at Month 3 for the Co-Ad and Month 5 for the Control group). | 
| Anti-pneumococcal Antibody Titers | Anti-pneumococcal antibody titers for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) were determined by Multiplex Opsonophagocytosis Assay (MOPA) | At one month post-dose 1 (Month 1) | 
| Adjusted Geometric Mean Concentrations (GMCs) for Anti-gE Antibody | Anti-gE antibody concentrations (GMCs) adjusted for age and baseline concentrations were determined using Analysis Of Covariance (ANCOVA) model. Adjusted GMCs were expressed in milli-international units per milliliter (mIU/mL) | One month post-dose 2 (at Month 3 for the Co-Ad and Month 5 for the Control group). | 
| Adjusted Geometric Mean Titers (GMTs) of Anti-pneumococcal Antibodies | Geometric mean antibody (anti-pneumococcal antibodies: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) titers adjusted for age and baseline concentration were determined using ANCOVA model. | At one month post-dose 1 (Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms by Vaccine and Dose | Assessed solicited local symptoms were pain, erythema and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 erythema/swelling = erythema/swelling that had spread beyond 100 millimeters (mm) of injection site. The Co-Ad Group received only 2 vaccine doses. | Within 7 days (Day 1 - 7) after each vaccination | 
| Number of Days With Each Solicited Local Symptoms | The number of days with any local symptoms had been assessed during the post-vaccination period. | Within 7 days (Day 1 - 7) after each vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, fever [defined as oral temperature ≥ 38.0 degrees Celsius (°C)/ 100.4 degrees Fahrenheit (°F)], GastroIntestinal (GI) symptoms, headache, myalgia and shivering. 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 (Day 1 - 7) after each vaccination | 
| Number of Days With Solicited General Symptoms | The number of days with any general symptoms had been assessed during the post-vaccination period. Assessed solicited general symptoms were fatigue, fever, GastroIntestinal (GI) symptoms, headache, myalgia and shivering. | Within 7 days (Day 1 - 7) after each vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AE) | An unsolicited AE covered 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. | Within 30 days (Day 1 to 30) after each vaccination | 
| Number of Subjects With Any and Related Serious Adverse Events (SAE) From Day 1 to 30 Days Post Last Vaccination | SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related SAEs= SAEs assessed by the investigator as causally related to the study vaccination. | From first vaccination at Day 1 up to 30 days post last vaccination | 
| Number of Subjects With Any and Related SAEs From 30 Days Post Last Vaccination up to Study End. | Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related SAEs= SAEs assessed by the investigator as causally related to the study vaccination. | From 30 days post last vaccination up to study end (Month 14 for the Co-Ad group and Month 16 for the Control group) | 
| Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs) From Day 1 to 30 Days Post Last Vaccination | pIMDs assessed were a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not had an autoimmune aetiology. Related pIMDs= pIMDs assessed by the investigator as causally related to the study vaccination. | From first vaccination at Day 1 up to 30 days post last vaccination. | 
| Number of Subjects With Any pIMDs From 30 Days Post Last Vaccination up to Study End. | pIMDs assessed were a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not had an autoimmune aetiology. | From 30 days post last vaccination up to study end (Month 14 for the Co-Ad group and Month 16 for the Control group) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms by Dose | Assessed solicited local symptoms were pain, erythema and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 erythema/swelling = erythema/swelling that had spread beyond 100 millimeters (mm) of injection site. The Co-Ad Group received only 2 vaccine doses. | Within 7 days (Day 1 - 7) after each vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Immunogenicity, Shingles, Adults, Prevenar 13, HZ