A Long-term Follow-up Study (ZOE-LTFU) of Two Studies 110390 (ZOSTER-006) and 113077 (ZOSTER-022) to Assess the Efficacy, Safety, and Immunogenicity Persistence of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine and Assessment of 1 or 2 Additional Doses in Two Subgroups of Older Adults

Study Overview
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Brief Summary
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The purpose of this study is a long-term follow-up of the two studies 110390 and 113077 (ZOSTER-006/022) to assess the efficacy, safety, and immunogenicity persistence of GSK Biologicals' Herpes Zoster subunit (HZ/su) vaccine and will include an assessment of 1 or 2 additional doses in two subgroups of older adults.

Detailed Description
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This is the long-term follow-up study (ZOE-LTFU) of studies 110390 and 113077 (ZOSTER-006/022) to assess the prophylactic efficacy, safety, and immunogenicity persistence of GSK Biologicals' Herpes Zoster subunit (HZ/su) vaccine and will include an assessment of 1 or 2 additional doses on a 0 or 0, 2-month schedule in two subgroups of older adults.

Official Title
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Efficacy, Safety and Immunogenicity of GSK Biologicals' HZ/su Vaccine GSK1437173A in a Phase IIIb, Open-label, Long-term Follow-up Study (ZOE-LTFU) of Studies 110390/113077 (ZOSTER-006/022) and Assessment of Additional Doses in Older Adults

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Herpes Zoster Vaccine GSK1437173A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits, ability to have scheduled contacts to allow evaluation during the study). Or subjects with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, availability for follow-up contacts). Written informed consent obtained from the subject prior to performance of any study specific procedure. Subject who participated in ZOSTER-006 or ZOSTER-022 studies and received at least one dose of HZ/su vaccine. Additional inclusion criteria for the 1-Additional Dose Revaccination and Control groups, ONLY: Female subjects of non-childbearing potential may be enrolled in this study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in this study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (pharmaceutical product or device) at the time of enrolment or planned use during the study period. Previous vaccination against Varicella Zoster Virus (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 the HZ/su vaccine administered in studies ZOSTER-006/022). Chronic administration (defined as ≥ 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to Visit Month 0 of study ZOSTER-049 or expected administration at any time during the study period. For corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent. A prednisone dose of < 20 mg/day is allowed. Inhaled, topical and intra-articular corticosteroids are allowed. Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab) within 6 months prior to Visit Month 0 of study ZOSTER-049 or expected administration at any time during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). Administration of immunoglobulins and/or any blood products within 3 months prior to Visit Month 0 of study ZOSTER-049 or planned administration during the study period. Prolonged use (> 14 consecutive days) of oral and/or parenteral antiviral agents that are active against VZV (acyclovir, valacyclovir, famciclovir, etc. ) and planned to be used during the study period for an indication other than to treat suspected or confirmed HZ or an HZ-related complication (topical use of these antiviral agents is allowed). Important underlying illness that in the opinion of the investigator would be expected to interfere significantly during the study. Additional exclusion criteria for the 1-Additional Dose Revaccination and Control groups, only: Subjects who experienced an SAE from first vaccination in the previous ZOSTER-006/022 studies to enrolment in study ZOSTER-049 that was considered related to study vaccine by either the investigator or the sponsor. Subjects with a new onset of a pIMD or exacerbation of a pIMD from first vaccination in the previous ZOSTER-006/022 studies to enrolment in study ZOSTER-049. Use of any investigational or non-registered product (pharmaceutical product or device) within 30 days preceding the first dose of study vaccine or planned use during the study period. Administration or planned administration of any other immunizations within 30 days before the first study vaccination or scheduled within 30 days after study vaccination. However, licensed non-replicating vaccines (i.e., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines for seasonal or pandemic flu, with or without adjuvant) may be administered up to 8 days prior to each dose and/or at least 14 days after any dose of study vaccine. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Additionally, consider allergic reactions to other material or equipment related to study participation (such as materials that may possibly contain latex-gloves, syringes, etc.). Please note, the vaccine and vials in this study do not contain latex. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential). Previous episode/history of HZ.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LTFU Group<br>Long-Term Follow-Up of the subjects who received at least one dose of the HZ/su vaccine in the primary studies ZOSTER-006/022 | Biological: Herpes Zoster Vaccine GSK1437173A<br>* Intramuscular injection<br>|
| Experimental: Additional Dose Group (1AdD Group)<br>Subjects who received 2 doses of the HZ/su vaccine in the primary studies ZOSTER-006/022 and will receive 1 additional dose of the HZ/su vaccine in the current study. | Biological: Herpes Zoster Vaccine GSK1437173A<br>* Intramuscular injection<br>|
| Experimental: Revaccination Group (Rev Group)<br>Subjects who received 2 doses of the HZ/su vaccine in the primary studies ZOSTER-006/022 and will receive 2 additional doses of the HZ/su vaccine in the current study on a 0, 2 Month schedule (N=60). | Biological: Herpes Zoster Vaccine GSK1437173A<br>* Intramuscular injection<br>|
| Sham Comparator: Control Group (Ctrl Group)<br>Subjects who received 2 doses of the HZ/su vaccine in the primary studies ZOSTER-006/022 and will receive no additional doses of the HZ/su vaccine in the current study and will control for the 1-Additional and Revaccination groups | Biological: Herpes Zoster Vaccine GSK1437173A<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with confirmed herpes zoster (HZ).cases | A suspected case of HZ can be confirmed in two ways: By Polymerase Chain Reaction (PCR) By the HZ Ascertainment Committee (HZAC) | During the entire study period (up to Month 72). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with confirmed herpes zoster (HZ) cases | A suspected case of HZ can be confirmed in two ways: By Polymerase Chain Reaction (PCR) By the HZ Ascertainment Committee (HZAC) | 1 month post dose 2 in the previous Z-006/022 studies to study end (Month 72). | 
| Number of subjects with confirmed post herpetic neuralgia (PHN) cases | PHN is defined by the presence of HZ-associated severe 'worst' pain persisting or appearing more than 90 days after onset of the HZ rash. | 1 month post dose 2 in the previous Z-006/022 studies to study end (Month 72). | 
| Number of HZ related complications (other than PHN) | HZ complications include: HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke. | For the total duration of the Zoster-049 study, i.e. from Month 1 post dose 2 in the previous Z-006/022 studies to study end (Month 72). | 
| Anti-glicoprotein E (gE) antibody (Ab) concentrations | Anti-gE Ab concentrations were expressed as geometric mean concentrations (GMCs), as determined by ELISA. | At Months 0, 12, 24, 36, 48, 60 and 72 (LTFU Haemagglutination Inhibition(HI) subset, 1-Additional Dose, Revaccination and Control groups), at Month 1 (1-Additional Dose, Revaccination and Control groups), and at Month 3 (Revaccination and Control groups | 
| Cell mediated immunity (CMI) in terms of frequencies of antigen-specific CD4+ T cells. | Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by Intracellular Cytokine Staining (ICS). | At Months 0, 12, 24, 36, 48, 60 and 72 (LTFU CMI subset, 1-Additional Dose, Revaccination and Control groups), at Month 1 (1-Additional Dose, Revaccination and Control groups), and at Month 3 (Revaccination and Control groups). | 
| Number of subjects with any, and Grade 3 solicited local symptoms | These symptoms were assessed in subjects administered with 1 or 2 additional doses of HZ/su vaccine. Assessed solicited local symptoms were pain, redness and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | Within 7 days (Days 0-6) after each vaccination. | 
| Number of subjects with any, Grade 3 and related solicited general symptoms | These symptoms were assessed in subjects administered with 1 or 2 additional doses of HZ/su vaccine. Assessed solicited general symptoms were fatigue, fever [defined as oral temperature equal to or above 37.5 degrees Celsius (°C)], gastrointestinal symptoms,headache, myalgia, and shivering.Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 7 days (Days 0-6) after each vaccination. | 
| Number of subjects with unsolicited adverse events (AEs) | These symptoms were assessed in subjects administered with 1 or 2 additional doses of HZ/su vaccine. An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 30 days (Days 0-29) after each vaccination. | 
| Number of subjects with any Serious adverse events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Month 0 to Month 12 (1-Additional Dose and Control groups) and from Month 0 until 12 months after last HZ/su vaccination (Revaccination group). | 
| Number of subjects with any SAEs related to investigational vaccine, related to study participation or to GSK concomitant medica-tion/vaccine. | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study (up to Month 72) | 
| Number of subjects with any and related Potential immune-mediated diseases (pIMDs). | Potential immune-mediated diseases (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 aetiology | From Month 0 to Month 12 (1-Additional Dose and Control groups) and from Month until 12 months after last HZ/su vaccination (Revaccination group). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, Immunogenicity, Safety, Adults, Herpes zoster