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

NCT01954251 | Completed Phase 3 Results

• 2 other identifiers: 1170362013-000372-15
• Study Type: interventional
• Target: 829
• Locations: 3 countries
• Sites: 20

Brief Summary

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.

Conditions

Herpes Zoster

Keywords

FLU-D-QIV; Adults; Safety; Immunogenicity; co-administration; Herpes zoster

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• Number of Subjects With FLU HI Antibody Titers ≥1:10

  At Day 0 (PRE) and 21 post vaccination

• Number of Seroprotected Subjects With HI Antibody Titers ≥ 1:40

  At Day 0 (PRE) and at Day 21 post vaccination

• FLU Haemagglutination Inhibition (HI) Antibody Titers

  At Day 0 (PRE) and Day 21 post vaccination

• Number of Seroconverted Subjects in Terms of HI Antibodies

  At Day 21 post vaccination

• Geometric Mean Ratio for Flu HI Antibodies Post-vaccination Titer

  At Day 21 post vaccination

Study Arms (2)

Co-Ad Group

EXPERIMENTAL

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; Biological: GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A

Control Group

ACTIVE COMPARATOR

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; Biological: GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A

Interventions

Herpes Zoster vaccine GSK 1437173A BIOLOGICAL

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

Co-Ad Group; Control Group

GSK Biologicals' quadrivalent seasonal influenza vaccine FLU-D-QIV GSK2321138A BIOLOGICAL

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

Also known as: Influsplit™ Tetra (Germany), Fluarix™ Quadrivalent (United States)

Co-Ad Group; Control Group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Phoenix, Arizona, 85018, United States

Location

GSK Investigational Site

Carnegie, Pennsylvania, 15106, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16508, United States

Location

GSK Investigational Site

Brampton, Ontario, L6T 0G1, Canada

Location

GSK Investigational Site

Toronto, Ontario, M9W 4L6, Canada

Location

GSK Investigational Site

Weinheim, Baden-Wurttemberg, 69469, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Flörsheim, Hesse, 65439, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45355, Germany

Location

GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

Location

GSK Investigational Site

Dippoldiswalde, Saxony, 01744, Germany

Location

GSK Investigational Site

Freiberg, Saxony, 09599, Germany

Location

GSK Investigational Site

Freital, Saxony, 01705, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23554, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 10629, Germany

Location

GSK Investigational Site

Berlin, 10717, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Berlin, 13125, Germany

Location

GSK Investigational Site

Berlin, 13347, Germany

Location

Related Publications (1)

• Schwarz TF, Aggarwal N, Moeckesch B, Schenkenberger I, Claeys C, Douha M, Godeaux O, Grupping K, Heineman TC, Fauqued ML, Oostvogels L, Van den Steen P, Lal H. Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older. J Infect Dis. 2017 Dec 12;216(11):1352-1361. doi: 10.1093/infdis/jix481.

  PMID: 29029224 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Herpes Zoster

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Limitations and Caveats

The current data reflect the data reported in the database at the time of the end-of-study analysis. The previous data were based on the primary analysis including a safety analysis up to the data lock point of 7-APR-2015.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: October 1, 2013
• Study Start: October 3, 2013
• Primary Completion: June 2, 2014
• Study Completion: March 20, 2015
• Last Updated: May 2, 2018
• Results First Posted: February 10, 2016

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

US (3); CA (2); DE (15)