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

Phase 3

Completed

Conditions: Herpes Zoster

Interventions: Biological: HZ/su vaccine (GSK1437173A)

Registration Number: NCT04176939

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study was 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 also assessed 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

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 exposed 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HZ/su Group	HZ/su vaccine (GSK1437173A)	Participants with renal transplant who completed the 2-dose Herpes Zoster (HZ/su) vaccination course in the primary ZOSTER-041 (NCT02058589) study were enrolled in the current ZOSTER-073 (NCT04176939) study. 47 of these participants further received 1 or 2 additional doses of HZ/su vaccine in the revaccination phase of the current ZOSTER-073 (NCT04176939) study, first dose at Month 24 and second dose at Month 25.

Primary Outcome Measures

Name	Time	Method
Anti-glycoprotein E (Anti-gE) Antibody Concentrations, as Assessed in the Long Term Follow-up (LTFU) Phase of the Current ZOSTER-073 Study	At Day 1, Month 12 and Month 24 (pre-revaccination) in the current ZOSTER-073 study	Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs) in milli-international units per milliliter (mIU/mL).
Anti-gE Antibody Concentrations, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	At Month 24 (pre-revaccination), Month 25 (1 month post-revaccination Dose 1) and Month 26 (1 month post-revaccination Dose 2) in the current ZOSTER-073 study	Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Secondary Outcome Measures

Name	Time	Method
Frequency of gE-specific Cluster of Differentiation 4 (CD4) (2+) T-cells, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	At Day 1, Month 12 and Month 24 (pre-revaccination) in the current ZOSTER-073 study	Frequency of gE-specific CD4 (2+) T-cells expressing two or more activation markers (from among interferon gamma \[IFN-γ\], interleukin-2 \[IL-2\], tumour necrosis factor alpha \[TNF-α\] and CD40 Ligand \[CD40L\]) was determined by intracellular cytokine staining (ICS) as measured by cytokine flow cytometry (CFC) and expressed in CD4(2+) T-cells per million cells \[CD4(2+) T-cells/million cells\].
Number of Participants With Serious Adverse Events (SAEs) Related to Primary Vaccination in ZOSTER-041 Study, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Month 13 (last visit) in ZOSTER-041 study until Month 24 in the current ZOSTER-073 study	SAEs assessed included any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study participant. SAEs related to primary vaccination in ZOSTER-041 study were assessed by the investigator.
Number of Participants With Suspected or Confirmed Herpes Zoster (HZ) Cases, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Month 13 (last visit) in ZOSTER-041 study until Day 1 (first visit) in the current ZOSTER-073 study	A suspected HZ case was defined as a new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) without alternative diagnosis. A confirmed HZ case was diagnosed by an algorithm that included Polymerase Chain Reaction (PCR) and the HZ Ascertainment Committee (HZAC) determination.
Number of Participants With Confirmed HZ Cases, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Day 1 until Month 24 in the current ZOSTER-073 study	A confirmed HZ case was diagnosed by an algorithm that included Polymerase Chain Reaction (PCR) and the HZ Ascertainment Committee (HZAC) determination.
Number of Participants With Suspected or Biopsy-proven Allograft Rejections, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Month 13 (last visit) in ZOSTER-041 study until Day 1 (first visit) in the current ZOSTER-073 study	The number of participants with biopsy for clinical indication (suspected) or surveillance protocol that was not biopsy-proven rejection and with biopsy-proven allograft rejections are reported. Biopsy-proven allograft rejections are defined as adverse events of specific interest (AESIs).
Number of Participants With Biopsy-proven Allograft Rejections, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Day 1 until Month 24 in the current ZOSTER-073 study	Biopsy-proven allograft rejection is defined as an adverse event of specific interest (AESI).
Number of Participants With Allograft Dysfunction Related to Allograft Rejection Episodes, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Month 13 (last visit) in ZOSTER-041 study until Month 24 in the current ZOSTER-073 study	Declining allograft function (allograft dysfunction) was 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 therapeutic immunosuppressive therapy. Allograft dysfunction is defined as having a fold increase in serum creatinine of 1.2 greater from the reference timepoint (2 months prior to an episode of biopsy-proven rejection).
Number of Participants With Allograft Dysfunction Related to HZ Episodes, as Assessed in the LTFU Phase of the Current ZOSTER-073 Study	From Month 13 (last visit) in ZOSTER-041 study until Month 24 in the current ZOSTER-073 study	Declining allograft function was 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. Allograft dysfunction is defined as having a fold increase in serum creatinine of 1.2 greater from the reference timepoint (2 months prior to an episode of HZ).
Frequency of gE-specific CD4(2+) T-cells, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	At Month 24 (pre-revaccination), Month 25 (1 month post-revaccination Dose 1) and Month 26 (1 month post-revaccination Dose 2) in the current ZOSTER-073 study	Frequency of gE-specific CD4 (2+) T-cells expressing two or more activation markers (from among IFN-γ, IL-2, TNF-α and CD40L) was determined by ICS as measured by CFC and expressed in CD4(2+) T-cells/million cells.
Anti-gE Antibody Concentrations, as Assessed in the Revaccination Follow-up Phase of the Current ZOSTER-073 Study	At Month 37 (12 months post-revaccination Dose 2) and Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	Persistence of humoral immunity after the revaccination course was evaluated in terms of anti-gE antibody concentrations. Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.
Frequency of gE-specific CD4(2+) T-cells, as Assessed in the Revaccination Follow-up Phase of the Current ZOSTER-073 Study	At Month 37 (12 months post-revaccination Dose 2) and Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	Frequency of gE-specific CD4 (2+) T-cells expressing two or more activation markers (from among IFN-γ, IL-2, TNF-α and CD40L) was determined by ICS as measured by CFC and expressed in CD4(2+) T-cells/million cells.
Number of Participants With Any and Grade 3 Solicited Administration Site Events After Each Revaccination, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	Within 7 days after each revaccination dose (administered at Month 24 [Dose 1] and at Month 25 [Dose 2]) in the current ZOSTER-073 study	Assessed solicited administration site events included erythema, pain and swelling at injection site. Any = occurrence of the event regardless of intensity grade. Any erythema/swelling at injection site = erythema/swelling at injection site with a diameter larger than (\>) 20 millimeters (mm). Grade 3 pain = significant pain at rest, which prevented normal, everyday activities. Grade 3 erythema/swelling at injection site = erythema/swelling at injection site with a diameter \>100 mm.
Duration in Days of Solicited Administration Site Events After Each Revaccination, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	Within 7 days after each revaccination dose (administered at Month 24 [Dose 1] and at Month 25 [Dose 2]) in the current ZOSTER-073 study	Duration is the number of days in which a participant experienced the solicited administration site event within the 7-day solicited follow-up period. Assessed solicited administration site events included erythema, pain and swelling at injection site.
Number of Participants With Any, Grade 3 and Related Solicited Systemic Events After Each Revaccination, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	Within 7 days after each revaccination dose (administered at Month 24 [Dose 1] and at Month 25 [Dose 2]) in the current ZOSTER-073 study	Assessed solicited systemic events included fatigue, gastrointestinal symptoms (including nausea, vomiting, diarrhea and/or abdominal pain), headache, myalgia, shivering and fever \[temperature higher than or equal (\>=) to 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F)\]. Any AE = occurrence of the event regardless of intensity grade. Grade 3 fatigue, gastrointestinal symptoms, headache, myalgia, shivering = event that prevented normal, everyday activities. Grade 3 fever = temperature higher (\>) than 39°C/102.2°F. Related fatigue, gastrointestinal symptoms, headache, myalgia, shivering, fever = event assessed by the investigator as related to the revaccination. The preferred route for measuring temperature in this study was oral.
Duration in Days of Solicited Systemic Events After Each Revaccination, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	Within 7 days after each revaccination dose (administered at Month 24 [Dose 1] and at Month 25 [Dose 2]) in the current ZOSTER-073 study	Duration is the number of days in which a participant experienced the solicited systemic event within the 7-day solicited follow-up period. Assessed solicited systemic events included fatigue, gastrointestinal symptoms (including nausea, vomiting, diarrhea and/or abdominal pain), headache, myalgia, shivering and fever.
Number of Participants With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) Post-revaccination, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	Within 30 days (across revaccination doses) post-revaccination period in the current ZOSTER-073 study	An unsolicited AE was defined as 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 was reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade or relation to revaccination. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as related to revaccination.
Number of Participants With Any Serious Adverse Events (SAEs) and Fatal SAEs, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 37 (12 months post-revaccination Dose 2) in the current ZOSTER-073 study	SAEs assessed included any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study participant. Any = occurrence of the SAE regardless of intensity grade or relation to revaccination. Fatal = SAE resulting in the death of the participant.
Number of Participants With Related SAEs and Related-fatal SAEs, as Assessed in the Revaccination Active Phase of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	SAEs assessed included any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study participant. Related = SAE assessed by the investigator as related to revaccination. Related-fatal = SAE resulting in the death of the participant assessed by the investigator as related to revaccination.
Number of Participants With Any and Related Biopsy-proven Allograft Rejections, as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	Biopsy-proven allograft rejection is defined as an adverse event of special interest (AESI) and is recorded in serious adverse event (SAE) screens, irrespective of the seriousness of the event. Related biopsy proven allograft rejections = biopsy-proven allograft rejections assessed by the investigator as related to revaccination.
Number of Participants With Any and Related Potential Immune-mediated Diseases (pIMDs), as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 37 (12 months post-revaccination Dose 2) in the current ZOSTER-073 study	pIMDs are defined as 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 = occurrence of the pIMD regardless of intensity grade or relation to revaccination. Related = pIMDs assessed by the investigator as related to revaccination.
Number of Participants With Confirmed HZ Cases, as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	A confirmed HZ case was diagnosed by an algorithm that included Polymerase Chain Reaction (PCR) and the HZ Ascertainment Committee (HZAC) determination.
Number of Participants With Allograft Dysfunction Following Revaccination, as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 37 (12 months post-revaccination Dose 2) in the current ZOSTER-073 study	Declining allograft function was assessed through all clinically obtained serum creatinine values from 3 months before the first revaccination dose until 3 months after the last revaccination dose. Allograft dysfunction is defined as having a fold increase in serum creatinine of 1.2 greater from the reference timepoint (3 months prior to revaccination).
Number of Participants With Allograft Dysfunction Related to Allograft Rejection, as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	Declining allograft function was 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 therapeutic immunosuppressive therapy. Allograft dysfunction is defined as having a fold increase in serum creatinine of 1.2 greater from the reference timepoint (2 months prior to an episode of biopsy-proven rejection).
Number of Participants With Allograft Dysfunction Related to HZ Episodes, as Assessed in the Revaccination Active and Follow-up Phases of the Current ZOSTER-073 Study	From Month 24 (pre-revaccination) until Month 49 (24 months post-revaccination Dose 2) in the current ZOSTER-073 study	Declining allograft function was 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. Allograft dysfunction is defined as having a fold increase in serum creatinine of 1.2 greater from the reference timepoint (2 months prior to an episode of HZ).