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.

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2015-001778-17-EE
• Date of registration: 08/02/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: 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.
• Scientific title: A phase IIIb, open-label, multi-country, multi-centre, 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 assessment of 1 or 2 additional doses on a 0 or 0, 2-month schedule in two subgroups of older adults. - ZOSTER-049 EXT:006-022
• Date of first enrolment: 01/03/2016
• Target sample size: 8581
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001778-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Factorial If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Historical Control Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Bioloigicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Bioloigicals

Key inclusion & exclusion criteria

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 com-pletion of the vaccination series.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1716
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6865

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 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 par-enteral 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;


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Vaccination against HZ and its related complications in adults older than 50 years (at the time of primary vaccination).
MedDRA version: 20.0 Level: LLT Classification code 10019982 Term: Herpes zoster NOS System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Herpes Zoster vaccine (GSK 1437173A)
Product Code: HZ/su
Pharmaceutical Form: Powder and suspension for suspension for injection
INN or Proposed INN: _
Current Sponsor code: gE
Other descriptive name: RECOMBINANT VARICELLA ZOSTER VIRUS SURFACE GLYCOPROTEIN E
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Number of confirmed HZ cases.
A suspected case of HZ can be confirmed in two ways:
•By Polymerase Chain Reaction (PCR)
•By the HZ Ascertainment Committee (HZAC)

Secondary Objective: VE in HZ prevention in subjects of each age*:
1 Z49
VE in HZ prevention in =50Y &*:
2 From 1 M p-D2 in Z6/22 to Z49 end
3 Over each Y from 1 M p-D2 in Z6/22
VE in PHN prevention in =50Y & *:
4 During Z49
5 From 1 M p-D2 in Z6/22 to Z49 end
VE in preventing HZ related complications (other than PHN) in =50Y & *
6 From D 1 in Z6/22
7 From 1 M p-D 2 in Z6/22 to Z49 end
I at Y 5-10 & beyond Z6/22 p-1’ vacc. in =50Y & *:
8 HI
9 CMI
I at Y 5-10 & beyond Z6/22 p-1’ vacc. in =50Y with conf. HZ:
10 HI
11 CMI
I at 1 M p-1st additional HZ/su D (1AdD** & Rev & Ctrl):
12 HI
13 CMI
I at 1 M p-2nd additional HZ/su D (Rev & Ctrl):
14 HI
15 CMI
I at Y 1-6 of Z49 (1AdD, Rev & Ctrl):
16 HI
17 CMI
18 Safety & reacto (1AdD & Rev)
19 Safety (LTFU & Ctrl)

*Ages: 50-59, 60-69, =60 & =70Y at Day 1 in Z6/22.
Y=year; M=Month D=Dose; p-=post; 1’=primary; I=Immuno; HI=Humoral Immuno; CMI=Cell-Mediated Immuno.
**Groups: 1AdD=1-Additional Dose; Rev=Revaccination; Ctrl=Control.

Timepoint(s) of evaluation of this end point: During the entire study period (up to Month 72).

Main Objective: To assess the Vaccine Efficacy (VE) in the prevention of Herpes Zoster (HZ) over the total duration of the ZOSTER-049 (Z49) study overall as measured by the reduction in HZ risk in subjects =50 years of age overall at the time of first vaccination in the ZOSTER-006/022 (Z6/22) studies.

Secondary Outcome(s)

Secondary end point(s): 1. Number of confirmed HZ cases.
A suspected case of HZ can be confirmed in two ways:
•By Polymerase Chain Reaction (PCR)
•By the HZ Ascertainment Committee (HZAC)

2. Number of Post-Herpetic Neuralgia (PHN) cases defined by the presence of HZ-associated severe ‘worst’ pain persisting or appearing more than 90 days after onset of the HZ rash.

3. Number of HZ related complications (other than PHN including HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke.

4. Anti-glycoprotein E (gE) antibody (Ab) concentrations expressed as geometric mean concentrations (GMCs), as determined by ELISA.

5. Cell mediated immunogenicity 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 Ne-crosis Factor alpha (TNF-a) and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by ICS).

6. 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.

7. Number of subjects with any, Grade 3 and related solicited general symptoms 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.

8. Number of subjects with unsolicited adverse events (AEs) 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.

9. Number of subjects with any Serious adverse events (SAEs) assessed including medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

10. Number of subjects with any SAEs related to investigational vaccine, related to study participation or to GSK concomitant medication/vaccine including medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

11. Number of subjects with any and related Potential immune-mediated diseases (pIMDs) that 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.

Timepoint(s) of evaluation of this end point: 1 and 2. 1 month post dose 2 in the previous Z-006/022 studies to study end (Month 72).

3. 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.

4 and 5. At months 0, 12, 24, 36, 48, 60 and 72 (LTFU HI and CMI subsets, 1-Add Dose, Revacc and Control groups), and at Month 1 (1-Add Dose, Revacc and Control groups), and at Month 3 (Revacc and Control groups).

6 and 7. Within 7 days (Days 0-6) after each vaccination.

8. During the 30 days (Days 0-29) after each vaccination.

9 and 11. From Month 0 to Month 12 (1-Add Dose and Control groups) and from Month 0 until 12 months after last HZ/su vaccination (Revacc group).

10. During the entire study During the entire study (up to Month 72).

Secondary ID(s)

2015-001778-17-FI

201190

Source(s) of Monetary Support

GlaxoSmithKline Biologicals

Ethics review

Status: Approved
Approval date: 15/02/2016
Contact: