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

Phase 3CompletedNCT01954251

GlaxoSmithKline829 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

829

Conditions

Herpes Zoster

Interventions

Herpes Zoster vaccine GSK 1437173ABIOLOGICAL

2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.

GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138ABIOLOGICAL

2 doses administered intramuscularly (IM) in the deltoid region of the dominant arm.

Eligibility

Sex: ALLMin age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (20)

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Carnegie, Pennsylvania, United States

Outcomes

Primary Outcomes

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).

Time frame: At one month post-dose 2 (Month 3)

Vaccine Response for Anti-gE Humoral Immunogenicity

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Within 7 days (Days 0-6) after each vaccine dose

Number of Subjects With Solicited General Symptoms

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From first vaccination up to Month 18 (study end)