A Study on the Long-term Efficacy, Safety and Persistence of Immune Response of a Vaccine Against Herpes Zoster in Older Adults

Study Overview
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Brief Summary
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The purpose of the current ZOSTER-101 long-term follow-up (LTFU) study of ZOSTER-049 (NCT02723773) study, an extension of ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) primary studies, is to assess the long-term vaccine efficacy (VE) against Herpes Zoster (HZ) (approximately 11-15 years post primary vaccination in ZOSTER-006/022 studies), persistence of immunogenicity and safety of GSK's Herpes Zoster subunit (HZ/su) vaccine in older adults. The persistence of immunogenicity and safety of 1 or 2 additional doses (0, 2-month schedule) of HZ/su vaccine administered to a small group of participants in ZOSTER-049 study (approximately 5 years after the initial vaccination in ZOSTER-006/022 studies) will also be assessed.

Official Title
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A Phase 3b, Open-label, Multi-country, Multi-centre, Long-term Follow-up Study of ZOSTER-049 (Follow-up of ZOSTER-006/022 Studies) to Assess the Prophylactic Efficacy, Safety and Persistence of Immune Response of a Herpes Zoster Subunit Vaccine and Assessment of Persistence of Immune Response and Safety of 1 or 2 Additional Doses Administered in ZOSTER-049 in 2 Subgroups of Older Adults

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: HZ/su vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants and participant's caregiver, who, in the opinion of the investigator, can and are willing to comply with the requirements of the protocol. Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure. Medically stable participants as established by medical history and clinical examination before entering into the study. Participants who completed ZOSTER-049 study (following at least 1 dose of HZ/su in ZOSTER-006/022 studies). Exclusion Criteria: Medical conditions Any clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant therapy Use of any investigational or non-registered product (drug, vaccine or medical device) for the treatment of HZ or Varicella Zoster Virus (VZV) infection at the time of enrolment or their planned use during the study period. Previous vaccination against VZV or HZ and/or planned administration during the study of a VZV or HZ vaccine (including an investigational or non-registered vaccine other than HZ/su administered in studies ZOSTER-006/022 or ZOSTER-049). Prior/Concurrent clinical study experience Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device) for the prevention and/or treatment of HZ or VZV and which may have a possible activity against VZV.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Interventional study model and allocation in the current study follow the same approach as presented in the primary studies.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: LTFU Group<br>Participants who received at least one dose of the HZ/su vaccine in the ZOSTER-006/022 primary studies and are followed for long-term vaccine efficacy and safety in the current ZOSTER-101 study. | Biological: HZ/su vaccine<br>* No study intervention is administered in this extension study. Participants received the HZ/su vaccine administered in the ZOSTER-049 (NCT02723773), ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) primary studies. In order to assess the persistence of immune responses, participants provide blood samples at Day 1 and yearly from Month 12 until Month 48 in the current ZOSTER-101 study, according to their study group assignment. In case of a suspected HZ case diagnosis in any of the participants, clinical specimens from HZ lesions (3 replicate samples, collected on the same day, per participant) are collected to confirm the diagnosis of HZ by Polymerase Chain Reaction (PCR)<br>|
| Other: 1-Additional Dose Group<br>Participants who received two doses of the HZ/su vaccine in the ZOSTER-006/022 primary studies and one additional dose of the HZ/su vaccine in the ZOSTER-049 study and are followed for persistence of immunogenicity and safety in the current ZOSTER-101 study. | Biological: HZ/su vaccine<br>* No study intervention is administered in this extension study. Participants received the HZ/su vaccine administered in the ZOSTER-049 (NCT02723773), ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) primary studies. In order to assess the persistence of immune responses, participants provide blood samples at Day 1 and yearly from Month 12 until Month 48 in the current ZOSTER-101 study, according to their study group assignment. In case of a suspected HZ case diagnosis in any of the participants, clinical specimens from HZ lesions (3 replicate samples, collected on the same day, per participant) are collected to confirm the diagnosis of HZ by Polymerase Chain Reaction (PCR)<br>|
| Other: Revaccination Group<br>Participants who received two doses of the HZ/su vaccine in the ZOSTER-006/022 primary studies and two additional doses of the HZ/su vaccine in the ZOSTER-049 study and are followed for persistence of immunogenicity and safety in the current ZOSTER-101 study. | Biological: HZ/su vaccine<br>* No study intervention is administered in this extension study. Participants received the HZ/su vaccine administered in the ZOSTER-049 (NCT02723773), ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) primary studies. In order to assess the persistence of immune responses, participants provide blood samples at Day 1 and yearly from Month 12 until Month 48 in the current ZOSTER-101 study, according to their study group assignment. In case of a suspected HZ case diagnosis in any of the participants, clinical specimens from HZ lesions (3 replicate samples, collected on the same day, per participant) are collected to confirm the diagnosis of HZ by Polymerase Chain Reaction (PCR)<br>|
| Other: Control Group<br>Participants who received two doses of the HZ/su vaccine in the ZOSTER-006/022 primary studies and no additional doses of the HZ/su vaccine in the ZOSTER-049 study, but who served as a control for the two groups that received 1 or 2 additional doses of HZ/su (1-Additional Dose and Revaccination groups). In the current ZOSTER-101 study, this Control group is used in the evaluation of the long-term vaccine efficacy, safety and as a control for persistence of immunogenicity to additional doses administered in ZOSTER-049 study. | Biological: HZ/su vaccine<br>* No study intervention is administered in this extension study. Participants received the HZ/su vaccine administered in the ZOSTER-049 (NCT02723773), ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) primary studies. In order to assess the persistence of immune responses, participants provide blood samples at Day 1 and yearly from Month 12 until Month 48 in the current ZOSTER-101 study, according to their study group assignment. In case of a suspected HZ case diagnosis in any of the participants, clinical specimens from HZ lesions (3 replicate samples, collected on the same day, per participant) are collected to confirm the diagnosis of HZ by Polymerase Chain Reaction (PCR)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants in LTFU and Control groups with confirmed HZ cases | A suspected case of HZ is defined as new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A suspected case of HZ can be confirmed in two ways: By PCR; By the HZ Ascertainment Committee (HZAC). | During the total duration of ZOSTER-101 study (Day 1 through Month 48) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants in LTFU and Control groups with confirmed HZ cases | A suspected case of HZ is defined as new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A suspected case of HZ can be confirmed in two ways: By PCR; By the HZAC. | From 1-month post-Dose 2 in the ZOSTER-006/022 studies until the end of the ZOSTER-101 study at Month 48 | 
| Anti-glycoprotein E (gE) antibody concentrations | Anti-gE antibody concentrations are expressed as geometric mean concentrations (GMCs), as determined by enzyme-linked immunosorbent assay (ELISA). | At Day 1, Months 12, 24, 36 and 48 in the ZOSTER-101 study | 
| Frequency of gE-specific Cluster of Differentiation (CD)4+ T-cells secreting at least two activation markers from among IFN-γ, IL-2, TNF-α, CD40L |  | At Day 1, Months 12, 24, 36 and 48 in the ZOSTER-101 study | 
| Percentage of participants with serious adverse events (SAEs) causally related to the study intervention | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity. Relationship between study intervention and the occurrence of SAEs is assessed by the investigator using clinical judgement. | During the total duration of the ZOSTER-101 study (Day 1 through Month 48) | 
| Percentage of participants with potential immune-mediated diseases (pIMDs) (serious and non-serious) causally related to the study intervention | pIMDs are a subset of adverse events of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. A serious pIMD is any pIMD that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity. Relationship between study intervention and the occurrence of pIMDs is assessed by the investigator using clinical judgement. | During the total duration of the ZOSTER-101 study (Day 1 through Month 48) | 
| Percentage of participants with HZ-related complications of confirmed HZ | A suspected case of HZ is defined as new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A suspected case of HZ can be confirmed in two ways: By PCR; By the HZAC. HZ complications are the following: post-herpetic neuralgia, HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke A. | During the total duration of the ZOSTER-101 study (Day 1 through Month 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shingles, Herpes Zoster subunit vaccine, Recombinant Zoster Vaccine (RZV), Long-term follow-up study, Long-term vaccine efficacy, Prophylactic efficacy, Safety, Persistence of immune response, Older adults