Back to resultsA Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response
Primary Purpose
Herpes Zoster
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
HZ/su vaccine (GSK1437173A)
Sponsored by
About this trial
This is an interventional prevention trial for Herpes Zoster
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria for enrolment
- Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol or/and subjects' Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
- Written informed consent obtained from the subject/LAR(s) of the subject prior to performance of any study-specific procedure.
- Subjects who previously participated in study ZOSTER-041 and completed the full 2 dose HZ/su primary vaccination course.
Inclusion criteria for revaccination
- Subjects receiving maintenance CIS therapy for the prevention of allograft rejection for a minimum of one month prior to the first revaccination.
- Subjects without an episode of allograft rejection within 90 days prior to the first revaccination visit.
- Female subjects of non-childbearing potential may be revaccinated. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
- Female subjects of childbearing potential may be revaccinated, if the subject:
- has practiced adequate contraception for 30 days prior to revaccination, and
- has a negative pregnancy test on the day of revaccination, and
- has agreed to continue adequate contraception up to 2 months after completion of the revaccination series.
Exclusion Criteria:
Exclusion criteria for enrolment Medical conditions
- Vaccination against HZ since completion of study ZOSTER-041.
- Significant underlying illness that, in the opinion of the investigator, is expected to prevent completion of the study.
- Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study.
Prior/Concurrent clinical study experience
• Concurrently participating in another interventional vaccine or immunosuppressive clinical study, in which the subject is ex-posed to an investigational or a non-investigational vaccine/product (drug) at any time during the ZOSTER-073 study.
Exclusion criteria for revaccination Medical conditions
- History of confirmed HZ within one year before revaccination visit (Visit 3).
- More than one organ transplanted.
- Any additional confirmed or suspected immunosuppressive or immunodeficient condition.
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
- Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study or make vaccination unsafe.
Prior/Concomitant therapy
- Administration or planned administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first revaccination dose of study vaccine and ending at Visit 5 (Month 26).
- Use of anti-CD20 or other B-cell monoclonal antibody agents as maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months of first revaccination dose of study vaccine.
- Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of maintenance immunosuppressive therapies.
- Planned administration/administration of a live vaccine in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration.
- Planned administration/administration of a non-replicating or subunit vaccine, not foreseen by the study protocol, in the period starting 8 days before and ending 30 days after each dose of study vaccine.
Other exclusion criteria for revaccination
- Pregnant or lactating female.
- Female planning to become pregnant or planning to discontinue contraceptive precautions up to 2 months post-revaccination Dose 2.
- Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- 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
HZ/su Group
Arm Description
Eligible participants who had a complete 2-dose HZ/su vaccination course in the primary study (NCT02058589) will be enrolled in this extension study, to receive 2 doses of HZ/su vaccine- first dose at Month 24 and second dose at Month 25 and will be followed up until the study end.
Outcomes
Primary Outcome Measures
Evaluation of persistence of humoral immunity in terms of anti-glycoprotein E (anti-gE) antibody concentrations as determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 1 in the Long Term Follow Up (LTFU) phase
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations, as determined by ELISA are presented as geometric mean concentrations (GMCs).
Anti-gE antibody concentrations as determined by ELISA at Month 12, in the LTFU phase
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Anti-gE antibody concentrations as determined by ELISA at Month 24, in the LTFU phase
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Anti-gE antibody concentrations as determined by ELISA at pre-revaccination, in the revaccination active phase
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination dose 1, in the revaccination active phase
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination Dose 2 in the revaccination active phase
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Secondary Outcome Measures
Evaluation of cell-mediated immune (CMI) responses in terms of frequencies of gE-specific CD4+ T-cells as determined by Intracellular Cytokine Staining (ICS) at day 1, in the LTFU phase
Determination of gE-specific CD4+ T-cells expressing two or more markers such as Interferon-gamma (IFN)-γ, IL-2, Tumour Necrosis Factor (TNF)-α, CD40L is performed by Intracellular Cytokine Staining (ICS) and presented as T-cells per million cells.
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 12, in the LTFU phase
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 24 in the LTFU phase
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by Intracellular Cytokine Staining (ICS) and presented as T-cells per million cells.
Percentage of subjects with any Serious Adverse Events (SAEs) related to primary vaccination in the LTFU phase
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
Number of subjects with history of suspected or confirmed Herpes Zoster (HZ) episode in the LTFU phase
A suspected HZ episode is defined as a new unilateral rash accompanied by pain broadly defined to include allodynia, pruritus or other sensations without alternative diagnosis.
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Number of subjects with a confirmed HZ episode in the LTFU phase
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Number of subjects with a history of suspected or biopsy-proven allograft rejections in the LTFU phase
Biopsy-proven allograft rejection is defined as an adverse event of special interest (AESI).
Number of subjects with biopsy-proven allograft rejections in the LTFU phase
Biopsy-proven allograft rejection is defined as an AESI.
Number of subjects with allograft dysfunction related to allograft rejection episodes in the LTFU phase
Declining allograft function (allograft dysfunction) is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Number of subjects with allograft dysfunction related to HZ episodes in the LTFU phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ rash resolution.
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at pre-vaccination in the Revaccination active phase
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 25 in the Revaccination active phase
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 26 in the Revaccination active phase
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Anti-gE antibody concentrations as determined by ELISA at 12 months post-revaccination Dose 2, in the Revaccination follow-up phase
Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Anti-gE antibody concentrations as determined by ELISA at 24 months post-revaccination Dose 2, in the Revaccination follow-up phase
Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 37 in the Revaccination follow-up phase
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 49 in the Revaccination follow-up phase
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Percentage of subjects with at least one solicited local Adverse event (AE) after each revaccination in the revaccination active and follow-up phases
Solicited local AEs are: Pain at injection site; Redness at injection site and Swelling at injection site. Any redness/swelling is scored as injection site redness/swelling with a diameter larger than (>) 20 millimeters (mm).
Percentage of subjects with any solicited general AE after each revaccination in the revaccination active and follow-up phases
Solicited general AEs are: Fatigue; Fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity); Gastrointestinal symptoms (including nausea, vomiting, diarrhea and/or abdominal pain); Headache; Myalgia and Shivering.
Percentage of subjects with any unsolicited AEs after each revaccination in the revaccination active and follow-up phases
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.
Percentage of subjects with any SAE, in the Revaccination active phase
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any SAE, including fatal SAEs are assessed.
Percentage of subjects with any SAE, in the Revaccination follow-up phase
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any SAE, including fatal SAEs are assessed.
Percentage of subjects with any related SAE, in the Revaccination active phase
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any related SAE, including related-fatal SAEs are assessed.
Percentage of subjects with any related SAE, in the Revaccination follow-up phase
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any related SAE, including related-fatal SAEs are assessed.
Number of subjects with biopsy-proven allograft rejections in the Revaccination active phase
Biopsy-proven allograft rejection is defined as an AESI. It will be recorded in SAE screens, irrespective of the seriousness of the event. All biopsy proven allograft rejections and its causal relationship to the vaccination is assessed.
Number of subjects with biopsy-proven allograft rejections in the Revaccination follow-up phase
Biopsy-proven allograft rejection is defined as an AESI. It will be recorded in SAE screens, irrespective of the seriousness of the event. All biopsy proven allograft rejections and its causal relationship to the vaccination is assessed.
Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination active phase
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 etiology. Any pIMDs and its causal relationship to revaccination are assessed.
Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination follow-up phase
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 etiology. Any pIMDs and its causal relationship to revaccination are assessed.
Number of subjects with a confirmed HZ episode in the Revaccination active phase
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Number of subjects with a confirmed HZ episode in the Revaccination follow-up phase
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Number of subjects with allograft dysfunction following revaccination in the revaccination active phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 3 months before the first revaccination dose until 3 months after the last revaccination dose. Data for this outcome measure is collected from month 21 to month 26 and analyzed from month 24-month 26 study visits.
Number of subjects with allograft dysfunction following revaccination in the revaccination follow-up phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 3 months before the first revaccination dose until 3 months after the last revaccination dose. Data for this outcome measure is collected from month 26 to month 28 and analyzed from month 26-month 37 study visits.
Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination active phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination follow-up phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination active phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ resolution.
Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination follow-up phase
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ resolution.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04176939
Brief Title
A Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response
Official Title
Long-term Immunogenicity Study of Herpes Zoster Subunit Vaccine (GSK1437173A) and Immunogenicity and Safety Assessment of Revaccination With Two Additional Doses in Adults With Renal Transplant From Study ZOSTER-041
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 9, 2019 (Actual)
Primary Completion Date
August 12, 2022 (Actual)
Study Completion Date
August 14, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the long-term immune responses to the Herpes Zoster subunit (HZ/su) vaccine as well as safety up to 7 years after the 2-dose primary vaccination course from study ZOSTER-041 (NCT02058589). This study will also assess immune responses as well as safety after revaccination with 2 additional doses of the HZ/su administered at 6 to 8 years after the 2-dose primary vaccination course.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HZ/su Group
Arm Type
Experimental
Arm Description
Eligible participants who had a complete 2-dose HZ/su vaccination course in the primary study (NCT02058589) will be enrolled in this extension study, to receive 2 doses of HZ/su vaccine- first dose at Month 24 and second dose at Month 25 and will be followed up until the study end.
Intervention Type
Biological
Intervention Name(s)
HZ/su vaccine (GSK1437173A)
Intervention Description
2 intramuscular (IM) doses of the HZ/su vaccine administered- first dose at month 24 and second dose at month 25
Primary Outcome Measure Information:
Title
Evaluation of persistence of humoral immunity in terms of anti-glycoprotein E (anti-gE) antibody concentrations as determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 1 in the Long Term Follow Up (LTFU) phase
Description
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations, as determined by ELISA are presented as geometric mean concentrations (GMCs).
Time Frame
At Day 1
Title
Anti-gE antibody concentrations as determined by ELISA at Month 12, in the LTFU phase
Description
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 12
Title
Anti-gE antibody concentrations as determined by ELISA at Month 24, in the LTFU phase
Description
Persistence of humoral immunity after the primary vaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 24
Title
Anti-gE antibody concentrations as determined by ELISA at pre-revaccination, in the revaccination active phase
Description
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 24 (pre-vaccination)
Title
Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination dose 1, in the revaccination active phase
Description
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 25
Title
Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination Dose 2 in the revaccination active phase
Description
Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 26
Secondary Outcome Measure Information:
Title
Evaluation of cell-mediated immune (CMI) responses in terms of frequencies of gE-specific CD4+ T-cells as determined by Intracellular Cytokine Staining (ICS) at day 1, in the LTFU phase
Description
Determination of gE-specific CD4+ T-cells expressing two or more markers such as Interferon-gamma (IFN)-γ, IL-2, Tumour Necrosis Factor (TNF)-α, CD40L is performed by Intracellular Cytokine Staining (ICS) and presented as T-cells per million cells.
Time Frame
At Day 1
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 12, in the LTFU phase
Description
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Time Frame
At Month 12
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 24 in the LTFU phase
Description
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by Intracellular Cytokine Staining (ICS) and presented as T-cells per million cells.
Time Frame
At Month 24
Title
Percentage of subjects with any Serious Adverse Events (SAEs) related to primary vaccination in the LTFU phase
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame
From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073)
Title
Number of subjects with history of suspected or confirmed Herpes Zoster (HZ) episode in the LTFU phase
Description
A suspected HZ episode is defined as a new unilateral rash accompanied by pain broadly defined to include allodynia, pruritus or other sensations without alternative diagnosis.
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Time Frame
From Month 13 (last visit in study ZOSTER-041) to Day 1 (Visit 1 in study ZOSTER-073)
Title
Number of subjects with a confirmed HZ episode in the LTFU phase
Description
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Time Frame
From Day 1 to Month 24
Title
Number of subjects with a history of suspected or biopsy-proven allograft rejections in the LTFU phase
Description
Biopsy-proven allograft rejection is defined as an adverse event of special interest (AESI).
Time Frame
From Month 13 (last visit in study ZOSTER-041) to Day 1 (Visit 1 in study ZOSTER-073)
Title
Number of subjects with biopsy-proven allograft rejections in the LTFU phase
Description
Biopsy-proven allograft rejection is defined as an AESI.
Time Frame
From Day 1 to Month 24
Title
Number of subjects with allograft dysfunction related to allograft rejection episodes in the LTFU phase
Description
Declining allograft function (allograft dysfunction) is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Time Frame
From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073)
Title
Number of subjects with allograft dysfunction related to HZ episodes in the LTFU phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ rash resolution.
Time Frame
From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073)
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at pre-vaccination in the Revaccination active phase
Description
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Time Frame
At Month 24 (pre-vaccination)
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 25 in the Revaccination active phase
Description
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Time Frame
At Month 25
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 26 in the Revaccination active phase
Description
Determination of gE-specific CD4+ T cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T- cells per million cells.
Time Frame
At Month 26
Title
Anti-gE antibody concentrations as determined by ELISA at 12 months post-revaccination Dose 2, in the Revaccination follow-up phase
Description
Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 37
Title
Anti-gE antibody concentrations as determined by ELISA at 24 months post-revaccination Dose 2, in the Revaccination follow-up phase
Description
Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.
Time Frame
At Month 49
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 37 in the Revaccination follow-up phase
Description
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Time Frame
At Month 37
Title
Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 49 in the Revaccination follow-up phase
Description
Determination of gE-specific CD4+ T-cells expressing two or more markers such as IFN-γ, IL-2, TNF-α, CD40L is performed by ICS and presented as T-cells per million cells.
Time Frame
At Month 49
Title
Percentage of subjects with at least one solicited local Adverse event (AE) after each revaccination in the revaccination active and follow-up phases
Description
Solicited local AEs are: Pain at injection site; Redness at injection site and Swelling at injection site. Any redness/swelling is scored as injection site redness/swelling with a diameter larger than (>) 20 millimeters (mm).
Time Frame
Within 7 days after each revaccination (Administered at Month 24 and Month 25)
Title
Percentage of subjects with any solicited general AE after each revaccination in the revaccination active and follow-up phases
Description
Solicited general AEs are: Fatigue; Fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity); Gastrointestinal symptoms (including nausea, vomiting, diarrhea and/or abdominal pain); Headache; Myalgia and Shivering.
Time Frame
Within 7 days after each revaccination (Administered at Month 24 and Month 25)
Title
Percentage of subjects with any unsolicited AEs after each revaccination in the revaccination active and follow-up phases
Description
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.
Time Frame
Within 30 days after each revaccination (Administered at Month 24 and Month 25)
Title
Percentage of subjects with any SAE, in the Revaccination active phase
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any SAE, including fatal SAEs are assessed.
Time Frame
From Month 24 to Month 26
Title
Percentage of subjects with any SAE, in the Revaccination follow-up phase
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any SAE, including fatal SAEs are assessed.
Time Frame
From Month 26 to Month 37
Title
Percentage of subjects with any related SAE, in the Revaccination active phase
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any related SAE, including related-fatal SAEs are assessed.
Time Frame
From Month 24 to Month 26
Title
Percentage of subjects with any related SAE, in the Revaccination follow-up phase
Description
SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any related SAE, including related-fatal SAEs are assessed.
Time Frame
From Month 26 to Month 49
Title
Number of subjects with biopsy-proven allograft rejections in the Revaccination active phase
Description
Biopsy-proven allograft rejection is defined as an AESI. It will be recorded in SAE screens, irrespective of the seriousness of the event. All biopsy proven allograft rejections and its causal relationship to the vaccination is assessed.
Time Frame
From Month 24 to Month 26
Title
Number of subjects with biopsy-proven allograft rejections in the Revaccination follow-up phase
Description
Biopsy-proven allograft rejection is defined as an AESI. It will be recorded in SAE screens, irrespective of the seriousness of the event. All biopsy proven allograft rejections and its causal relationship to the vaccination is assessed.
Time Frame
From Month 26 to Month 49
Title
Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination active phase
Description
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 etiology. Any pIMDs and its causal relationship to revaccination are assessed.
Time Frame
From Month 24 to Month 26
Title
Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination follow-up phase
Description
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 etiology. Any pIMDs and its causal relationship to revaccination are assessed.
Time Frame
From Month 26 to Month 37
Title
Number of subjects with a confirmed HZ episode in the Revaccination active phase
Description
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Time Frame
From Month 24 to Month 26
Title
Number of subjects with a confirmed HZ episode in the Revaccination follow-up phase
Description
A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.
Time Frame
From Month 26 to Month 49
Title
Number of subjects with allograft dysfunction following revaccination in the revaccination active phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 3 months before the first revaccination dose until 3 months after the last revaccination dose. Data for this outcome measure is collected from month 21 to month 26 and analyzed from month 24-month 26 study visits.
Time Frame
From Month 24 to Month 26
Title
Number of subjects with allograft dysfunction following revaccination in the revaccination follow-up phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 3 months before the first revaccination dose until 3 months after the last revaccination dose. Data for this outcome measure is collected from month 26 to month 28 and analyzed from month 26-month 37 study visits.
Time Frame
From Month 26 to Month 37
Title
Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination active phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Time Frame
From Month 24 to Month 26
Title
Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination follow-up phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of biopsy-proven rejection and up to 2 months after rejection resolution and cessation of high dose of immunosuppressive therapy.
Time Frame
From Month 26 to Month 49
Title
Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination active phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ resolution.
Time Frame
From Month 24 to Month 26
Title
Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination follow-up phase
Description
Declining allograft function is assessed through all clinically obtained serum creatinine values from 2 months prior to an episode of HZ and up to 2 months after HZ resolution.
Time Frame
From Month 26 to Month 49
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria for enrolment
Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol or/and subjects' Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
Written informed consent obtained from the subject/LAR(s) of the subject prior to performance of any study-specific procedure.
Subjects who previously participated in study ZOSTER-041 and completed the full 2 dose HZ/su primary vaccination course.
Inclusion criteria for revaccination
Subjects receiving maintenance CIS therapy for the prevention of allograft rejection for a minimum of one month prior to the first revaccination.
Subjects without an episode of allograft rejection within 90 days prior to the first revaccination visit.
Female subjects of non-childbearing potential may be revaccinated. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
Female subjects of childbearing potential may be revaccinated, if the subject:
has practiced adequate contraception for 30 days prior to revaccination, and
has a negative pregnancy test on the day of revaccination, and
has agreed to continue adequate contraception up to 2 months after completion of the revaccination series.
Exclusion Criteria:
Exclusion criteria for enrolment Medical conditions
Vaccination against HZ since completion of study ZOSTER-041.
Significant underlying illness that, in the opinion of the investigator, is expected to prevent completion of the study.
Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study.
Prior/Concurrent clinical study experience
• Concurrently participating in another interventional vaccine or immunosuppressive clinical study, in which the subject is ex-posed to an investigational or a non-investigational vaccine/product (drug) at any time during the ZOSTER-073 study.
Exclusion criteria for revaccination Medical conditions
History of confirmed HZ within one year before revaccination visit (Visit 3).
More than one organ transplanted.
Any additional confirmed or suspected immunosuppressive or immunodeficient condition.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study or make vaccination unsafe.
Prior/Concomitant therapy
Administration or planned administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first revaccination dose of study vaccine and ending at Visit 5 (Month 26).
Use of anti-CD20 or other B-cell monoclonal antibody agents as maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months of first revaccination dose of study vaccine.
Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of maintenance immunosuppressive therapies.
Planned administration/administration of a live vaccine in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration.
Planned administration/administration of a non-replicating or subunit vaccine, not foreseen by the study protocol, in the period starting 8 days before and ending 30 days after each dose of study vaccine.
Other exclusion criteria for revaccination
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions up to 2 months post-revaccination Dose 2.
Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
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
Bruxelles
ZIP/Postal Code
1090
Country
Belgium
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
GSK Investigational Site
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
GSK Investigational Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Panama
ZIP/Postal Code
1001
Country
Panama
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
GSK Investigational Site
City
Hospitalet de Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
GSK Investigational Site
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
GSK Investigational Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
GSK Investigational Site
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
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 will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
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://www.clinicalstudydatarequest.com
Learn more about this trial
A Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response
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