Clinical Trials Register

Summary
EudraCT Number:	2015-001778-17
Sponsor's Protocol Code Number:	201190
National Competent Authority:	Estonia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-02-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Estonia - SAM

A.2

EudraCT number

2015-001778-17

A.3

Full title of the trial

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.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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.

A.3.2

Name or abbreviated title of the trial where available

ZOSTER-049 EXT:006-022

A.4.1

Sponsor's protocol code number

201190

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Bioloigicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l'institut 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Herpes Zoster vaccine (GSK 1437173A)
D.3.2	Product code	HZ/su
D.3.4	Pharmaceutical form	Powder and suspension for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	_
D.3.9.2	Current sponsor code	gE
D.3.9.3	Other descriptive name	RECOMBINANT VARICELLA ZOSTER VIRUS SURFACE GLYCOPROTEIN E
D.3.9.4	EV Substance Code	SUB31416
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Vaccination against HZ and its related complications in adults older than 50 years (at the time of primary vaccination).

E.1.1.1

Medical condition in easily understood language

Herpes zoster (Shingles) disease.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019982
E.1.2	Term	Herpes zoster NOS
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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;
•Pregnant or lactating female;
•Female planning to become pregnant or planning to discon-tinue contraceptive precautions (if of childbearing potential);
•Previous episode/history of HZ.

E.5 End points

E.5.1

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)

E.5.1.1

Timepoint(s) of evaluation of this end point

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

E.5.2

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-γ) and/or Interleukin-2 (IL-2) and/or Tumour Ne-crosis Factor alpha (TNF-α) 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.

E.5.2.1

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).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

reactogenicity, immunogenicity.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Factorial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Historical Control

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Canada

Czech Republic

Estonia

Finland

France

Germany

Hong Kong

Italy

Japan

Korea, Republic of

Mexico

Spain

Sweden

Taiwan

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Visit Last Subject or Last Contact Last Subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

824

F.4.2

For a multinational trial

F.4.2.1

In the EEA

5458

F.4.2.2

In the whole clinical trial

8581

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

A plan for treatment or care after the subject has ended the participation in the trial is not provided for prophylactic vaccine studies, as the subjects are healthy and do not need any treatment or care after end of the study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-06-28

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