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Trial record 2 of 2 for:    NCT02058589

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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ClinicalTrials.gov Identifier: NCT04176939
Recruitment Status : Active, not recruiting
First Posted : November 25, 2019
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Herpes Zoster Biological: HZ/su vaccine (GSK1437173A) Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : December 9, 2019
Estimated Primary Completion Date : April 8, 2024
Estimated Study Completion Date : April 8, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Shingles
MedlinePlus related topics: Shingles

Arm Intervention/treatment
Experimental: HZ/su Group
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.
Biological: HZ/su vaccine (GSK1437173A)
2 intramuscular (IM) doses of the HZ/su vaccine administered- first dose at month 24 and second dose at month 25




Primary Outcome Measures :
  1. 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 [ Time Frame: At Day 1 ]
    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).

  2. Anti-gE antibody concentrations as determined by ELISA at Month 12, in the LTFU phase [ Time Frame: At Month 12 ]
    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.

  3. Anti-gE antibody concentrations as determined by ELISA at Month 24, in the LTFU phase [ Time Frame: At Month 24 ]
    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.

  4. Anti-gE antibody concentrations as determined by ELISA at pre-revaccination, in the revaccination active phase [ Time Frame: At Month 24 (pre-vaccination) ]
    Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.

  5. Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination dose 1, in the revaccination active phase [ Time Frame: At Month 25 ]
    Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.

  6. Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination Dose 2 in the revaccination active phase [ Time Frame: At Month 26 ]
    Anti-gE antibody concentrations as determined by ELISA are presented as GMCs.


Secondary Outcome Measures :
  1. 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 [ Time Frame: At Day 1 ]
    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.

  2. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 12, in the LTFU phase [ Time Frame: At Month 12 ]
    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.

  3. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 24 in the LTFU phase [ Time Frame: At Month 24 ]
    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.

  4. Percentage of subjects with any Serious Adverse Events (SAEs) related to primary vaccination in the LTFU phase [ Time Frame: From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073) ]
    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.

  5. Number of subjects with history of suspected or confirmed Herpes Zoster (HZ) episode in the LTFU phase [ Time Frame: From Month 13 (last visit in study ZOSTER-041) to Day 1 (Visit 1 in study ZOSTER-073) ]

    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.


  6. Number of subjects with a confirmed HZ episode in the LTFU phase [ Time Frame: From Day 1 to Month 24 ]
    A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.

  7. Number of subjects with a history of suspected or biopsy-proven allograft rejections in the LTFU phase [ Time Frame: From Month 13 (last visit in study ZOSTER-041) to Day 1 (Visit 1 in study ZOSTER-073) ]
    Biopsy-proven allograft rejection is defined as an adverse event of special interest (AESI).

  8. Number of subjects with biopsy-proven allograft rejections in the LTFU phase [ Time Frame: From Day 1 to Month 24 ]
    Biopsy-proven allograft rejection is defined as an AESI.

  9. Number of subjects with allograft dysfunction related to allograft rejection episodes in the LTFU phase [ Time Frame: From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073) ]
    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.

  10. Number of subjects with allograft dysfunction related to HZ episodes in the LTFU phase [ Time Frame: From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073) ]
    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.

  11. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at pre-vaccination in the Revaccination active phase [ Time Frame: At Month 24 (pre-vaccination) ]
    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.

  12. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 25 in the Revaccination active phase [ Time Frame: At Month 25 ]
    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.

  13. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 26 in the Revaccination active phase [ Time Frame: At Month 26 ]
    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.

  14. Anti-gE antibody concentrations as determined by ELISA at 12 months post-revaccination Dose 2, in the Revaccination follow-up phase [ Time Frame: At Month 37 ]
    Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.

  15. Anti-gE antibody concentrations as determined by ELISA at 24 months post-revaccination Dose 2, in the Revaccination follow-up phase [ Time Frame: At Month 49 ]
    Persistence of humoral immunity after the revaccination course evaluated in terms of anti-gE antibody concentrations as determined by ELISA are presented as GMCs.

  16. Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 37 in the Revaccination follow-up phase [ Time Frame: At Month 37 ]
    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.

  17. Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 49 in the Revaccination follow-up phase [ Time Frame: At Month 49 ]
    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.

  18. Percentage of subjects with at least one solicited local Adverse event (AE) after each revaccination in the revaccination active and follow-up phases [ Time Frame: Within 7 days after each revaccination (Administered at Month 24 and Month 25) ]
    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).

  19. Percentage of subjects with any solicited general AE after each revaccination in the revaccination active and follow-up phases [ Time Frame: Within 7 days after each revaccination (Administered at Month 24 and Month 25) ]
    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.

  20. Percentage of subjects with any unsolicited AEs after each revaccination in the revaccination active and follow-up phases [ Time Frame: Within 30 days after each revaccination (Administered at Month 24 and Month 25) ]
    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.

  21. Percentage of subjects with any SAE, in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  22. Percentage of subjects with any SAE, in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 37 ]
    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.

  23. Percentage of subjects with any related SAE, in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  24. Percentage of subjects with any related SAE, in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 49 ]
    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.

  25. Number of subjects with biopsy-proven allograft rejections in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  26. Number of subjects with biopsy-proven allograft rejections in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 49 ]
    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.

  27. Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  28. Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 37 ]
    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.

  29. Number of subjects with a confirmed HZ episode in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.

  30. Number of subjects with a confirmed HZ episode in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 49 ]
    A confirmed HZ episode is diagnosed by Polymerase Chain Reaction (PCR), or by the HZ Ascertainment Committee (HZAC) determination.

  31. Number of subjects with allograft dysfunction following revaccination in the revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  32. Number of subjects with allograft dysfunction following revaccination in the revaccination follow-up phase [ Time Frame: From Month 26 to Month 37 ]
    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.

  33. Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  34. Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 49 ]
    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.

  35. Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination active phase [ Time Frame: From Month 24 to Month 26 ]
    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.

  36. Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination follow-up phase [ Time Frame: From Month 26 to Month 49 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04176939


Locations
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Belgium
GSK Investigational Site
Bruxelles, Belgium, 1090
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5B 1W8
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2N2
Finland
GSK Investigational Site
Helsinki, Finland, 00029
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 06351
GSK Investigational Site
Seoul, Korea, Republic of, 137-701
Panama
GSK Investigational Site
Panama, Panama, 1001
Spain
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Hospitalet de Llobregat, Spain, 08907
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Santander, Spain, 39008
GSK Investigational Site
Sevilla, Spain, 41013
Taiwan
GSK Investigational Site
Taoyuan, Taiwan, 333
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04176939    
Other Study ID Numbers: 212340
2019-001815-21 ( EudraCT Number )
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: July 21, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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.
URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Herpes Zoster
Varicella Zoster Virus Infection
Herpesviridae Infections
DNA Virus Infections
Virus Diseases