Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Intramuscularly in Adults Aged ≥50 Years

Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Versus Intramuscularly in Adults Aged 50 Years or Older

The purpose of this study is to assess the immunogenicity, safety, and reactogenicity of GSK Biologicals' Herpes Zoster (HZ) vaccine (GSK 1437173A) when administered subcutaneously (SC) as compared to intramuscularly (IM) to people 50 years of age and older.

Study Overview

• Status: Completed
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: Herpes zoster vaccine GSK1437173A

Detailed Description

There are 2 treatment groups in this study based upon the mode of vaccine administration.

The humoral immunogenicity (HI) will be measured in all subjects.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-0025
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Subject, residing in Japan, is of Japanese ethnic origin, defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese.
• Subject has provided written informed consent.
• Subject, male or female, who is 50 YOA or older at the time of the first vaccination.
• Subject, if female, of non-childbearing potential may be enrolled in the study.

• Subject, if female, 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 (i.e., for 2 months after Month 2).
• Exclusion Criteria:
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Concurrently participating or planned participation 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 product.
• Administration or planned administration of a live vaccine within 30 days prior to the first study vaccination through 30 days after the second study vaccination.
• Administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
• Planned administration, during the study, of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
• Administration of immunoglobulins and/or any blood products within the three (3) months preceding the first dose of study vaccine or planned administration during the study period.

• Chronic administration (defined as >14 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

  • For corticosteroids, a prednisone dose of <20 mg/day, or equivalent, is allowed.
  • Inhaled, topical, and intra-articular corticosteroids are allowed.
• Administration or planned administration of long-acting immune-modifying drugs (e.g., infliximab) within six months prior to the first vaccine dose through the duration of the study period.
• History of HZ.
• Previous vaccination against HZ or varicella (registered or investigational product).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.
• Significant underlying illness that, in the opinion of the investigator, would be expected to prevent completion of the study.
• Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.

• Acute disease and/or fever at the time of vaccination:

  • Fever is defined as temperature ≥37.5°C (99.5°F) for oral, axillary, or tympanic route, or ≥38.0°C/100.4°F for 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.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) through Month 4 (i.e., 2 months after the second dose of study vaccine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SC HZ/su Group; Subjects will receive HZ/su vaccine administered SC on a 0,2-month schedule.	Biological: Herpes zoster vaccine GSK1437173A; HZ/su vaccine administered either into the subcutaneous tissue of the upper arm (deltoid region) of the non-dominant arm or intramuscularly in the deltoid region of non-dominant arm on a 0,2-month schedule.
Active Comparator: IM HZ/su Group; Subjects will receive HZ/su vaccine administered IM on a 0,2-month schedule.	Biological: Herpes zoster vaccine GSK1437173A; HZ/su vaccine administered either into the subcutaneous tissue of the upper arm (deltoid region) of the non-dominant arm or intramuscularly in the deltoid region of non-dominant arm on a 0,2-month schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-Glycoprotein E (Anti-gE) Antibody Concentrations Higher Than or Equal to (≥)18 Milli-international Units Per Milliliter (mIU/mL)	A seropositive subject was defined as a subject whose anti-gE Ab concentration was greater than or equal to the assay cut-off value, of 18 mIU/mL.	Before vaccination (PRE), two months after Dose 1 (M2) and one month after Dose 2 (M3)
Anti-gE Antibody Concentrations	Anti-gE antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL.	Before vaccination (PRE), two months after Dose 1 (M2) and one month after Dose 2 (M3)
Number of Subjects With Vaccine Response for Anti-gE Antibody Concentrations	Vaccine response was defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x18 mIU/mL); for initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.	At two months after Dose 1 (M2) and one month after Dose 2 (M3)
Descriptive Statistics of Anti-gE Antibody Concentrations	Anti-gE antibody concentrations were assessed by the Enzyme Lynked Immunosorbent Assay.	Before vaccination (PRE), at two months after dose 1 (M2) and one month after Dose 2 (M3)
Number of Subjects With Solicited Local Symptoms	The solicited local symptoms assessed were: Arm movement/range of motion of the vaccinated arm, Injection site pruritus, Pain, Redness, and Swelling. Any = occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Significant pain at rest that prevented normal every day activities. Grade 3 Injection site pruritus = Significant pruritus that prevented normal every day activities. Grade 3 impairment of arm movement/range of motion = Significant impairment of arm movement/range of motion that prevented normal every day activities.	During the 7 day (Days 0-6) post vaccination, after each dose (D) and across doses
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms were: Fatigue, Fever, Gastrointestinal (nausea, vomiting, diarrhea and/or abdominal pain), Headache, Myalgia, and Shivering. Fever = axillary temperature ≥37.5°C. Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 Fever = axillary temperature higher than (>) 39.0°C. Related = general symptom assessed by the investigator as causally related to vaccination.	During the 7 day (Days 0-6) post vaccination, after each dose (D) and across doses
Mean Number of Days With Local Symptoms	Days with solicited local symptoms were tabulated for the total vaccinated cohort.	During the 7 day (Days 0-6) post vaccination, after each dose (D)
Mean Number of Days With General Symptoms	Days with solicited general symptoms were tabulated for the total vaccinated cohort.	During the 7 day (Days 0-6) post vaccination, after each dose (D)
Number of Subjects With Potential Immune-Mediated Disorders (pIMDs)	Potential immune-mediated diseases (pIMDs) were 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 Month 0 to Month 3
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.	Within 30 days (Days 0-29) post vaccination period
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 Month 0 to Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-gE Antibody Concentrations ≥ 97 mIU/mL	A seropositive subject was defined as a subject whose anti-gE Ab concentration was greater than or equal to the assay cut-off value of 97 mIU/mL.	At Month 14
Anti-gE Antibody Concentrations	Anti-gE antibody concentrations were expressed as geometric mean concnetrations (GMCs) and measured in mIU/mL.	At Month 14
Number of Subjects With Vaccine Response for Anti-gE Antibody Concentrations	Vaccine response was 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.	Twelve Months after Dose 2 (M14)
Number of Subjects With pIMDs	Potential immune-mediated diseases (pIMDs) were 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.	Up to Month 14 post vaccination period
Number of Subjects With 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.	Up to Month 14 post vaccination period

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Vink P, Shiramoto M, Ogawa M, Eda M, Douha M, Heineman T, Lal H. Safety and immunogenicity of a Herpes Zoster subunit vaccine in Japanese population aged >/=50 years when administered subcutaneously vs. intramuscularly. Hum Vaccin Immunother. 2017 Mar 4;13(3):574-578. doi: 10.1080/21645515.2016.1232787. Epub 2016 Dec 9.

Helpful 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.

Study record dates

Study Major Dates

• Study Start: June 17, 2013
• Primary Completion (Actual): October 10, 2013
• Study Completion (Actual): November 11, 2014

Study Registration Dates

• First Submitted: January 24, 2013
• First Submitted That Met QC Criteria: January 24, 2013
• First Posted (Estimate): January 28, 2013

Study Record Updates

• Last Update Posted (Actual): October 25, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Elderly; Safety; Adults; Immunogenicity; Subcutaneous; Herpes Zoster; Intramuscular; ≥50 years of age
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster; Herpes Simplex
• Other Study ID Numbers: 116760; 2012-005671-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 116760
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register