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

Herpes Zoster Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02723773
• Other study ID #: 201190
• Secondary ID: 2015-001778-17
• Status: Completed
• Phase: Phase 3
• Start date: April 18, 2016
• Est. completion date: June 28, 2023

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7541
• Est. completion date: June 28, 2023
• Est. primary completion date: June 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Zoster

Intervention

Biological:
• Herpes Zoster Vaccine GSK1437173A
Intramuscular injection

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Geelong	Victoria
Australia	GSK Investigational Site	Westmead	New South Wales
Australia	GSK Investigational Site	Wollongong	New South Wales
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Gatineau	Quebec
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Mirabel	Quebec
Canada	GSK Investigational Site	Pointe-Claire	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Québec City	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Victoria	British Columbia
Canada	GSK Investigational Site	Woodstock	Ontario
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Ceske Budejovice
Czechia	GSK Investigational Site	Hradec Kralove
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Finland	GSK Investigational Site	Espoo
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Jarvenpaa
Finland	GSK Investigational Site	Kokkola
Finland	GSK Investigational Site	Oulu
Finland	GSK Investigational Site	Pori
Finland	GSK Investigational Site	Seinajoki
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Château Gontier
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Laval
France	GSK Investigational Site	Montrevault
France	GSK Investigational Site	Muret
France	GSK Investigational Site	Murs-Erigne
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Rosiers d'Egletons
France	GSK Investigational Site	Segré
France	GSK Investigational Site	Tours
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dachau	Bayern
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Floersheim	Hessen
Germany	GSK Investigational Site	Freiberg	Sachsen
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Gueglingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koethen	Sachsen-Anhalt
Germany	GSK Investigational Site	Kuenzing	Bayern
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Rednitzhembach	Bayern
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wallerfing	Bayern
Germany	GSK Investigational Site	Wangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wuerzburg	Bayern
Hong Kong	GSK Investigational Site	Kwun Tong
Hong Kong	GSK Investigational Site	Shatin
Italy	GSK Investigational Site	Chieti	Abruzzo
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Monza	Lombardia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Sassari	Sardegna
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Ansan
Korea, Republic of	GSK Investigational Site	Bucheon-si,
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Kangwon-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Zapopan, Jalisco	Jalisco
Spain	GSK Investigational Site	Alcover( Tarragona)
Spain	GSK Investigational Site	Balenyà (Barcelona)
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Centelles (Barcelona)
Spain	GSK Investigational Site	La Roca Del Valles (Barcelona)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda( Madrid
Spain	GSK Investigational Site	Peralada( Girona)
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vic
Sweden	GSK Investigational Site	Borås
Sweden	GSK Investigational Site	Eskilstuna
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Jönköping
Sweden	GSK Investigational Site	Karlskrona
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Upplands Väsby
Sweden	GSK Investigational Site	Uppsala
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan County
United Kingdom	GSK Investigational Site	Atherstone	Warwickshire
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Bradford on Avon	Wiltshire
United Kingdom	GSK Investigational Site	Broughshane
United Kingdom	GSK Investigational Site	Buckshaw Village, Chorley	Lancashire
United Kingdom	GSK Investigational Site	Liverpool
United States	GSK Investigational Site	Beachwood	Ohio
United States	GSK Investigational Site	Boise	Idaho
United States	GSK Investigational Site	Bristol	Tennessee
United States	GSK Investigational Site	Cary	North Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Elkridge	Maryland
United States	GSK Investigational Site	Glendale	Arizona
United States	GSK Investigational Site	Greer	South Carolina
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Mount Pleasant	South Carolina
United States	GSK Investigational Site	Murray	Utah
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Salisbury	North Carolina
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Spring Valley	California
United States	GSK Investigational Site	Uniontown	Pennsylvania
United States	GSK Investigational Site	Wadsworth	Ohio
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (1)

Strezova A, Diez-Domingo J, Al Shawafi K, Tinoco JC, Shi M, Pirrotta P, Mwakingwe-Omari A; Zoster-049 Study Group. Long-term Protection Against Herpes Zoster by the Adjuvanted Recombinant Zoster Vaccine: Interim Efficacy, Immunogenicity, and Safety Results up to 10 Years After Initial Vaccination. Open Forum Infect Dis. 2022 Oct 23;9(10):ofac485. doi: 10.1093/ofid/ofac485. eCollection 2022 Oct. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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
Secondary	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-?) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-a) 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).
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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).
Secondary	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)
Secondary	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).