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

Phase 3

Completed

• Conditions: Herpes Zoster
• Interventions: Biological: Herpes Zoster Vaccine GSK1437173A

• Registration Number: NCT02723773
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-03-10
• Study First Submitted QC: 2016-03-24
• Study First Posted: 2016-03-30
• Study Start: 2016-04-18
• Primary Completion: 2023-06-28
• Study Completion: 2023-06-28
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7541

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
1-Additional Dose Group	Herpes Zoster Vaccine GSK1437173A	Participants who received 2 doses of the HZ/su vaccine in the ZOSTER-006/022 primary studies received 1 additional dose of the HZ/su vaccine at Month 0 in the current ZOSTER-049:EXT 006-022 study.
Revaccination Group	Herpes Zoster Vaccine GSK1437173A	Participants who received 2 doses of the HZ/su vaccine in the ZOSTER-006/022 primary studies were revaccinated with 2 additional doses of the HZ/su vaccine at Month 0 and Month 2 in the current ZOSTER-049:EXT 006-022 study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Having at Least One Confirmed Herpes Zoster (HZ) Case During the Total Duration of ZOSTER-049:EXT 006-022 Study, Overall	During the total duration of ZOSTER-049:EXT 006-022 study (From Month 0 to Month 72)	A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by Polymerase Chain Reaction (PCR) and/or by HZ Ascertainment Committee (HZAC) determination, as per the algorithm pre-specified in the protocol.; As pre-specified in the protocol: * due to the high VE observed in ZOSTER-006/022 studies, recipients of placebo in both studies were offered cross-vaccination with HZ/su. Since there was no placebo group in this study, historic controls were used for VE assessment. Incidence rates estimations on Historical Control group were done by utilizing Poisson regression model using placebo data from ZOSTER-006/022 studies to obtain the coefficients by age ranges.; * the participants in Control group were a subset of LTFU group that were randomized to serve as control for those who were vaccinated in this study, otherwise they were treated similarly as LTFU group, hence LTFU and Control groups were combined.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Having at Least One Confirmed HZ Case During the Total Duration of ZOSTER-049:EXT 006-022 Study, by Age Ranges	During the total duration of ZOSTER-049:EXT 006-022 study (From Month 0 to Month 72)	A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Number of Participants Having at Least One Confirmed HZ Case From One Month Post-Dose 2 in ZOSTER-006/022 Studies Until the End of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	From one month post-Dose 2 (Month 3) in ZOSTER-006/022 primary studies until the end of ZOSTER-049:EXT 006-022 study (Month 72), a period of approximately 12 years	A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.; As pre-specified in the protocol: - participants from the Placebo groups in the ZOSTER-006/022 studies for Year 1 through Year 4 preceding the ZOSTER-049 EXT:006-022 study start and from the hypothetical Historical control group in the ZOSTER-049:EXT 006-022 study for Year 6 and onwards were combined in the Placebo/Historical control group.
Number of Participants Having at Least One Confirmed HZ Case Over the Follow-up Years From One Month Post-Dose 2 in ZOSTER-006/022 Studies Until the End of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	Over the follow-up years (Year 1, Year 2, Year 3, Year 4, Year 6, Year 7, Year 8, Year 9, Year 10 and Year 11) from one month post-Dose 2 (Month 3) in ZOSTER-006/022 primary studies until the end of ZOSTER-049:EXT 006-022 study (Month 72)	A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.; Confirmed HZ cases data was not collected for the participants included in the HZ/su and Placebo/Historical control groups during Year 5, as this was a gap year between end of ZOSTER-006/-022 studies and start of ZOSTER-049:EXT-006-022 study.; Results from the ZOSTER-006/022 studies were pooled for each year after vaccination with methods used in these studies. For overlapping years between ZOSTER-006/022 studies and this study, all the data were pooled. For the non-overlapping years only the data from ZOSTER-049:EXT 006-022 study was used.
Number of Participants Having at Least One Post-herpetic Neuralgia (PHN) Case During the Total Duration of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	During the total duration of ZOSTER-049:EXT 006-022 study (From Month 0 to Month 72)	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. Severe worst pain is defined as HZ-associated pain rated as 3 or greater on the worst pain question on the Zoster Brief Pain Inventory (ZBPI) questionnaire. The ZBPI questionnaire uses a 0 to 10 point numeric and visual intensity scale, in which 0 represents the minimum value and 10 the maximum value on the scale. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Number of Participants Having at Least One PHN Case From One Month Post-Dose 2 in ZOSTER-006/022 Primary Studies Until the End of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	From one month post-Dose 2 (Month 3) in ZOSTER-006/022 primary studies until the end of ZOSTER-049:EXT 006-022 study (Month 72), a period of approximately 12 years	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. Severe worst pain is defined as HZ-associated pain rated as 3 or greater on the worst pain question on the Zoster Brief Pain Inventory (ZBPI) questionnaire. The ZBPI questionnaire uses a 0 to 10 point numeric and visual intensity scale, in which 0 represents the minimum value and 10 the maximum value on the scale. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Number of Participants Having at Least One HZ Related Complications (Other Than PHN) Case During the Total Duration of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	During the total duration of ZOSTER-049:EXT 006-022 study (From Month 0 to Month 72)	HZ complications include HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke. If a recorded complication was associated with a case of suspected HZ, and that case was finally not considered to be a confirmed case, the associated complication would not be considered as a complication of HZ. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Number of Participants Having at Least One HZ Related Complications (Other Than PHN) Case From One Month Post-dose 2 (Month 3) in ZOSTER-006/022 Primary Studies Until the End of ZOSTER-049:EXT 006-022 Study, Overall and by Age Ranges	From one month post-Dose 2 (Month 3) in ZOSTER-006/022 primary studies until the end of ZOSTER-049:EXT 006-022 study (Month 72), a period of approximately 12 years	HZ complications include HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke. If a recorded complication was associated with a case of suspected HZ, and that case was finally not considered to be a confirmed case, the associated complication would not be considered as a complication of HZ. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Anti-glycoprotein (gE) Antibody Concentrations for Humoral Immunity (HI) Subset at Years 5, 6, 7, 8, 9, 10, 11 and 12 After the Primary Vaccination in ZOSTER-006/022 Studies, Overall and by Age Ranges in the LTFU Group	At Years 5, 6, 7, 8, 9, 10, 11 and 12 after the primary vaccination in ZOSTER-006/022 studies	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). The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Frequency of Antigen-specific CD4 (2+) T-cells for Cell Mediated Immunity (CMI) Subset at Years 5, 6, 7, 8, 9, 10, 11 and 12 After the Primary Vaccination in ZOSTER-006/022 Studies, Overall and by Age Ranges in the LTFU Group	At Years 5, 6, 7, 8, 9, 10, 11 and 12 after the primary vaccination in ZOSTER-006/022 studies	Frequency of CD4 (2+) 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 was determined by Intracellular Cytokine Staining (ICS) and expressed in CD4 (2+) T-cells/million cells. The age ranges assessed were: \>=50 YOA (overall), 50-59 YOA, 60-69 YOA, \>=60 YOA and \>=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.
Anti-gE Antibody Concentrations for Participants in LTFU+Control >=50 YOA Group (With a Confirmed HZ Episode) at Years 5, 6, 7, 8, 9, 10, 11 and 12 After the Primary Vaccination in ZOSTER-006/022 Studies	At Years 5, 6, 7, 8, 9, 10, 11 and 12 after the primary vaccination in ZOSTER-006/022 studies	Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.
Frequency of Antigen-specific CD4 (2+) T-cells for Participants in LTFU+Control >=50 YOA Group (With a Confirmed HZ Episode) at Years 5, 6, 7, 8, 9 and 10 After the Primary Vaccination in ZOSTER-006/022 Studies	At Years 5, 6, 7, 8, 9, and 10 after the primary vaccination in ZOSTER-006/022 studies	Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.
Anti-gE Antibody Concentrations for 1-Additional Dose, Revaccination and Control Groups at Month 1 in the Current ZOSTER-049:EXT 006-022 Study	At Month 1 in the current ZOSTER-049:EXT 006-022 study	Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.
Frequency of Antigen-specific CD4(2+) T-cells for 1-Additional Dose, Revaccination and Control Groups at Month 1 in the Current ZOSTER-049:EXT 006-022 Study	At Month 1 in the current ZOSTER-049:EXT 006-022 study	Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.
Anti-gE Antibody Concentrations for Revaccination and Control Groups at Month 3 in the Current ZOSTER-049:EXT 006-022 Study	At Month 3 in the current ZOSTER-049:EXT 006-022 study	Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.
Frequency of Antigen-specific CD4 (2+) T-cells for Revaccination and Control Groups at Month 3 in the Current ZOSTER-049:EXT 006-022 Study	At Month 3 in the current ZOSTER-049:EXT 006-022 study	Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.
Anti-gE Antibody Concentrations for 1 Additional Dose, Revaccination and Control Groups at Month 0 and Years 1, 2, 3, 4, 5 and 6 in the Current ZOSTER-049:EXT 006-022 Study	At Month 0 and Years 1, 2, 3, 4, 5 and 6 in the current ZOSTER-049:EXT 006-022 study	Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.
Frequency of Antigen-specific CD4(2+) T-cells for 1-Additional Dose, Revaccination and Control Groups at Month 0 and Years 1, 2, 3, 4, 5 and 6 in the Current ZOSTER-049:EXT 006-022 Study	At Month 0 and Years 1, 2, 3, 4, 5 and 6 in the current ZOSTER-049:EXT 006-022 study	Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.
Number of Participants With Any and Grade 3 Solicited Local Symptoms	Within 7 days after each vaccination (vaccination occurring at Month 0 for 1-Additional Dose Group and at Months 0 and 2 for Revaccination Group) in the current ZOSTER-049:EXT 006-022 study	The assessed solicited local symptoms included pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Duration in Days of Solicited Local Symptoms	Within 7 days after each vaccination (vaccination occurring at Month 0 for 1-Additional Dose Group and at Months 0 and 2 for Revaccination Group) in the current ZOSTER-049:EXT 006-022 study	Duration is the number of days in which a participant experienced the symptom within the 7-day solicited follow-up period. The assessed solicited local symptoms included pain, redness and swelling.
Number of Participants With Any, Grade 3 and Related Solicited General Symptoms	Within 7 days after each vaccination (vaccination occurring at Month 0 for 1-Additional Dose Group and at Months 0 and 2 for Revaccination Group) in the current ZOSTER-049:EXT 006-022 study	The assessed solicited general symptoms included fatigue, fever \[defined as oral temperature \>=37.5 degrees Celsius (°C)\], gastrointestinal symptoms, headache, myalgia, and shivering. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. 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.
Duration in Days of Solicited General Symptoms	Within 7 days after each vaccination (vaccination occurring at Month 0 for 1-Additional Dose Group and at Months 0 and 2 for Revaccination Group) in the current ZOSTER-049:EXT 006-022 study	Duration is the number of days in which a participant experienced the symptom within the 7-day solicited follow-up period. The assessed solicited general symptoms included fatigue, fever \[defined as oral temperature \>=37.5°C\], gastrointestinal symptoms, headache, myalgia, and shivering.
Number of Participants With Any Unsolicited Adverse Events (AEs)	Within 30 days after any vaccination (vaccination occurring at Month 0 for 1-Additional Dose Group and at Months 0 and 2 for Revaccination Group) in the current ZOSTER-049:EXT 006-022 study	An unsolicited AE is defined as 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 = occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Participants With Any and Related Serious Adverse Events (SAEs)	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)	An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant. Any SAE = occurrence of the SAE regardless of intensity or relation to study vaccination. Related SAE = SAE assessed by the investigator as related to vaccination.
Number of Participants With SAEs Related to Investigational Vaccine, Related to Study Participation or to GSK Concomitant Medication/Vaccine	During the total duration of ZOSTER-049:EXT 006-022 study (from Month 0 to Month 72)	An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant.
Number of Participants With Any and Related Potential Immune-mediated Diseases (pIMDs)	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)	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 aetiology. Any pIMDs = occurrence of a pIMD regardless of relation to vaccination. Related pIMD = a pIMD assessed by the investigator as related to the study vaccination.

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 Liverpool, United Kingdom