Back to resultsStudy to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine at 9 and 10 Years After Vaccine Administration and Assessment of Re-vaccination With 2 Additional Doses at 10 Years After Initial Vaccination, in Healthy Subjects Aged 60 Years of Age(YOA) and Older
Primary Purpose
Herpes Zoster
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Herpes Zoster Vaccine GSK1437173A
Sponsored by
About this trial
This is an interventional prevention trial for Herpes Zoster focused on measuring Immunogenicity, Safety, Long term follow-up, Adults, Herpes zoster
Eligibility Criteria
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, ability to have scheduled contacts to allow evaluation during the study). Or subjects with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, vaccination visits, availability for follow-up contacts).
- Written informed consent obtained from the subject prior to performance of any study specific procedure.
- Previous participation in study ZOSTER-003 (NCT00434577), in group 50 µg gE / AS01B, and who completed the vaccination course (2 doses of HZ/su) in study ZOSTER-003 (NCT00434577).
- Subjects are expected to enter the study (or complete Visit 1) as of the time they turn 108 months after first vaccination of previous vaccination course with HZ/su and not later than 111 months.
Exclusion Criteria:
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first study visit (Day -29 to Day 0), or planned use during the study period.
- Use or anticipated use of immunosuppressants or 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 (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection).
- Administration or planned administration of a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine* within 8 days prior to or within 14 days after either dose of study vaccine.
E.g., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines and pneumococcal conjugate vaccines.
- Previous vaccination against HZ since initial vaccination in Zoster-003.
- Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study start, or planned administration during the study period.
- History of previous HZ.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSK1437173A vaccine Group
Arm Description
Subjects who completed vaccination course of 2 doses of HZ/su vaccine (group 50 μg gE/AS01B) in the study Zoster-003 (NCT00434577) were included in this study. 62 of these subjects further received 1 or 2 additional doses of HZ/su vaccine in the revaccination phase of this study
Outcomes
Primary Outcome Measures
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations
Anti-glycoprotein E (gE) Ab concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micro international units per milliliter (mIU/mL).
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations
Anti-gE Ab concentrations were determined by ELISA, presented as GMCs and expressed in mIU/mL.
Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.
gE specific CD4 (2+) T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L, were determined by means of Intracellular Cytokine Staining (ICS) and expressed in T-cells/million cells.
Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.
gE specific CD4 (2+)T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L were determined by means of ICS and expressed in T-cells/million cells.
Secondary Outcome Measures
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations by Each Age Category
Anti-gE Ab concentrations as determined by ELISA by each age category (60-69 years of age [YOA] and ≥70 YOA at the time of initial vaccination).Antibody concentrations were presented as GMCs and expressed in mIU/mL.
Frequencies of Antigen-specific CD4 (2+) T-cells by Each Age Category
Antigen specific CD4 (2+) T-cells as determined by means of ICS and expressed in T-cells/million cells, by each age category (60-69 YOA and ≥ 70 YOA at the time of initial vaccination).
Number of Subjects With Any Serious Adverse Events (SAEs) Related to Study Participation or to a Concurrent GSK Medication/Vaccine (Including GSK1437173A Administered During the Zoster-003 [NCT00434577] Study).
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Anti-gE Specific Antibody (Ab) Concentrations
Anti-gE antibody concentrations were determined by ELISA in all subjects, presented as GMCs and expressed in mIU/mL.
Frequencies of Antigen-specific CD4 (2+) T-cells, Post Re-vaccination Course.
Antigen specific CD4 (2+)T cells were determined by means of ICS and expressed in T-cells/million cells.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.
Assessed solicited local symptoms included: pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, prevented normal every day activities. Grade 3 redness/swelling = symptoms spreading beyond a surface of (>) 100 millimeters (mm).
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.
Assessed solicited general symptoms included: fatigue, gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, shivering and temperature [higher than or equal to (≥) 37.5 degrees Celsius (°C) for axillary, oral or tympanic route] and ≥38.0°C for rectal route. Grade 3 fatigue, gastrointestinal symptoms, headache, myalgia, shivering = symptoms that prevented normal activity. Grade 3 temperature = defined as fever higher than (>) 39.0°C, regardless of the route used.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) According to the Medical Dictionary for Regulatory Activities (MedDRA) Classification in All Subjects.
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 is 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.
Number of Subjects With Any, Related and Fatal SAEs.
SAEs assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs).
pIMDs assessed includes AEs that were autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Related pIMDs= pIMDs assessed by the investigator as related to the vaccination.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02735915
Brief Title
Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine at 9 and 10 Years After Vaccine Administration and Assessment of Re-vaccination With 2 Additional Doses at 10 Years After Initial Vaccination, in Healthy Subjects Aged 60 Years of Age(YOA) and Older
Official Title
Long Term Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine 1437173A and Assessment of Re-vaccination With 2 Additional Doses, in Healthy Subjects Aged 60 Years of Age and Older
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
April 11, 2016 (Actual)
Primary Completion Date
August 28, 2017 (Actual)
Study Completion Date
October 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to evaluate the persistence of immune response to the HZ vaccine as well as safety up to 10 years after the first dose of initial vaccination course. This study will also assess immune responses after re-vaccination with 2 additional doses of the HZ/su administered at ten years after first dose of initial vaccination course from study Zoster-003 (NCT00434577).
Detailed Description
In this LTFU study (ZOSTER-060), subjects who received 2 doses of HZ/su in the earlier Zoster-003 (NCT00434577) study will be followed up at Month 108/Year 9 and Month 120/Year 10 post first dose of vaccine for safety and immunogenicity (humoral and cellular). In order to assess the effect of re-vaccination with 2 additional doses of HZ/su vaccine, all the subjects will receive 2 additional doses of the HZ/su vaccine, on a 0, 2-month schedule at ten years after the initial vaccination course in study Zoster-003 (NCT00434577), and will be followed for reactogenicity, safety and humoral and cellular immunogenicity (including persistence).
In alignment with the previous persistence timepoints, this study has no control group.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Zoster
Keywords
Immunogenicity, Safety, Long term follow-up, Adults, Herpes zoster
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK1437173A vaccine Group
Arm Type
Experimental
Arm Description
Subjects who completed vaccination course of 2 doses of HZ/su vaccine (group 50 μg gE/AS01B) in the study Zoster-003 (NCT00434577) were included in this study. 62 of these subjects further received 1 or 2 additional doses of HZ/su vaccine in the revaccination phase of this study
Intervention Type
Biological
Intervention Name(s)
Herpes Zoster Vaccine GSK1437173A
Other Intervention Name(s)
HZ/su
Intervention Description
Intramuscular injection
Primary Outcome Measure Information:
Title
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations
Description
Anti-glycoprotein E (gE) Ab concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micro international units per milliliter (mIU/mL).
Time Frame
At Month 108 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations
Description
Anti-gE Ab concentrations were determined by ELISA, presented as GMCs and expressed in mIU/mL.
Time Frame
At Month 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.
Description
gE specific CD4 (2+) T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L, were determined by means of Intracellular Cytokine Staining (ICS) and expressed in T-cells/million cells.
Time Frame
At Month 108 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.
Description
gE specific CD4 (2+)T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L were determined by means of ICS and expressed in T-cells/million cells.
Time Frame
At Month 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Secondary Outcome Measure Information:
Title
Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations by Each Age Category
Description
Anti-gE Ab concentrations as determined by ELISA by each age category (60-69 years of age [YOA] and ≥70 YOA at the time of initial vaccination).Antibody concentrations were presented as GMCs and expressed in mIU/mL.
Time Frame
At Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Frequencies of Antigen-specific CD4 (2+) T-cells by Each Age Category
Description
Antigen specific CD4 (2+) T-cells as determined by means of ICS and expressed in T-cells/million cells, by each age category (60-69 YOA and ≥ 70 YOA at the time of initial vaccination).
Time Frame
At Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Number of Subjects With Any Serious Adverse Events (SAEs) Related to Study Participation or to a Concurrent GSK Medication/Vaccine (Including GSK1437173A Administered During the Zoster-003 [NCT00434577] Study).
Description
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
Between Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).
Title
Anti-gE Specific Antibody (Ab) Concentrations
Description
Anti-gE antibody concentrations were determined by ELISA in all subjects, presented as GMCs and expressed in mIU/mL.
Time Frame
At 1 month post each re-vaccination dose (i.e. Month 121 and Month 123) and at 1 year post last re-vaccination dose (i.e., Month 134).
Title
Frequencies of Antigen-specific CD4 (2+) T-cells, Post Re-vaccination Course.
Description
Antigen specific CD4 (2+)T cells were determined by means of ICS and expressed in T-cells/million cells.
Time Frame
At 1 month post each re-vaccination dose (i.e. Month 121 and Month 123) and at 1 year post last re-vaccination dose (i.e., Month 134).
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.
Description
Assessed solicited local symptoms included: pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, prevented normal every day activities. Grade 3 redness/swelling = symptoms spreading beyond a surface of (>) 100 millimeters (mm).
Time Frame
Within 7 days (Days 0-6) after each vaccination and across doses, in the current study.
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.
Description
Assessed solicited general symptoms included: fatigue, gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, shivering and temperature [higher than or equal to (≥) 37.5 degrees Celsius (°C) for axillary, oral or tympanic route] and ≥38.0°C for rectal route. Grade 3 fatigue, gastrointestinal symptoms, headache, myalgia, shivering = symptoms that prevented normal activity. Grade 3 temperature = defined as fever higher than (>) 39.0°C, regardless of the route used.
Time Frame
Within 7 days (Days 0-6) after each vaccination and across doses, in the current study.
Title
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) According to the Medical Dictionary for Regulatory Activities (MedDRA) Classification in All Subjects.
Description
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 is 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
Within 30 days (Days 0-29) after each vaccination in the current study.
Title
Number of Subjects With Any, Related and Fatal SAEs.
Description
SAEs assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time Frame
From Dose 1 of re-vaccination (Month 120) until study end (Month 134).
Title
Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs).
Description
pIMDs assessed includes AEs that were autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Related pIMDs= pIMDs assessed by the investigator as related to the vaccination.
Time Frame
From Dose 1 of re-vaccination (Month 120) until study end (Month 134).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
68 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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, ability to have scheduled contacts to allow evaluation during the study). Or subjects with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, vaccination visits, availability for follow-up contacts).
Written informed consent obtained from the subject prior to performance of any study specific procedure.
Previous participation in study ZOSTER-003 (NCT00434577), in group 50 µg gE / AS01B, and who completed the vaccination course (2 doses of HZ/su) in study ZOSTER-003 (NCT00434577).
Subjects are expected to enter the study (or complete Visit 1) as of the time they turn 108 months after first vaccination of previous vaccination course with HZ/su and not later than 111 months.
Exclusion Criteria:
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first study visit (Day -29 to Day 0), or planned use during the study period.
Use or anticipated use of immunosuppressants or 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 (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection).
Administration or planned administration of a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine* within 8 days prior to or within 14 days after either dose of study vaccine.
E.g., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines and pneumococcal conjugate vaccines.
Previous vaccination against HZ since initial vaccination in Zoster-003.
Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study start, or planned administration during the study period.
History of previous HZ.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Hradec Kralove
Country
Czechia
Facility Name
GSK Investigational Site
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68161
Country
Germany
Facility Name
GSK Investigational Site
City
Wuerzburg
State/Province
Bayern
ZIP/Postal Code
97070
Country
Germany
Facility Name
GSK Investigational Site
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45359
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13347
Country
Germany
Facility Name
GSK Investigational Site
City
Eskilstuna
ZIP/Postal Code
SE-631 88
Country
Sweden
Facility Name
GSK Investigational Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://clinicalstudydatarequest.com
Citations:
PubMed Identifier
29461919
Citation
Schwarz TF, Volpe S, Catteau G, Chlibek R, David MP, Richardus JH, Lal H, Oostvogels L, Pauksens K, Ravault S, Rombo L, Sonder G, Smetana J, Heineman T, Bastidas A. Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults. Hum Vaccin Immunother. 2018 Jun 3;14(6):1370-1377. doi: 10.1080/21645515.2018.1442162. Epub 2018 Mar 21.
Results Reference
background
PubMed Identifier
32502272
Citation
Hastie A, Catteau G, Enemuo A, Mrkvan T, Salaun B, Volpe S, Smetana J, Rombo L, Schwarz T, Pauksens K, Herve C, Bastidas A, Schuind A. Immunogenicity of the Adjuvanted Recombinant Zoster Vaccine: Persistence and Anamnestic Response to Additional Doses Administered 10 Years After Primary Vaccination. J Infect Dis. 2021 Dec 15;224(12):2025-2034. doi: 10.1093/infdis/jiaa300.
Results Reference
derived
Links:
URL
https://clinicalstudydatarequest.com
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Learn more about this trial
Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine at 9 and 10 Years After Vaccine Administration and Assessment of Re-vaccination With 2 Additional Doses at 10 Years After Initial Vaccination, in Healthy Subjects Aged 60 Years of Age(YOA) and Older
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