Clinical Trials Register

Summary
EudraCT Number:	2012-005671-14
Sponsor's Protocol Code Number:	116760
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-07
Trial results	View 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

UK - MHRA

A.2

EudraCT number

2012-005671-14

A.3

Full title of the trial

A phase III, randomised, open-label, multicentre clinical trial to assess the safety and immunogenicity of GSK Biologicals’ HZ/su candidate vaccine when administered subcutaneously as compared to intramuscularly according to a 0,2-month schedule in adults aged 50 years and older.

A.3.1

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

Safety and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ Herpes Zoster (HZ) vaccine when administered under the skin (subcutaneously) vs. into a muscle (intramuscularly) in adults 50 years of age and older.

A.3.2

Name or abbreviated title of the trial where available

ZOSTER-032

A.4.1

Sponsor's protocol code number

116760

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01777321

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 Biologicals
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	442089904460
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 (GSK1437173A)
D.3.2	Product code	HZ/su
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use Subcutaneous 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	gE antigen
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

Healthy volunteers (Prevention of Herpes Zoster [HZ] and related complications in adults ≥50 years of age [YOA] and immunocompromised adults ≥18 YOA)

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10019974
E.1.2	Term	Herpes zoster
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	HLT
E.1.2	Classification code	10019972
E.1.2	Term	Herpes viral infections
E.1.2	System Organ Class	10021881 - Infections and infestations

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 demonstrate non-inferiority in terms of the vaccine response rate (VRR) to the GSK Biologicals’ Herpes Zoster subunit (HZ/su) candidate vaccine (based on humoral immunogenicity [HI] response) when administered by subcutaneous (SC) injection compared to intramuscular (IM) injection to subjects ≥50 YOA at Month 3 in all subjects
• To demonstrate non-inferiority in terms of HI of the HZ/su candidate vaccine when administered by SC compared to IM injection to subjects ≥50 YOA at Month 3 in all subjects
• To evaluate safety and reactogenicity of the HZ/su candidate vaccine when administered by SC injection to subjects ≥50 YOA up to Month 3

E.2.2

Secondary objectives of the trial

•To demonstrate non-inferiority in terms of HI of the HZ/su candidate vaccine when administered by SC compared to IM injection to subjects ≥50 YOA at Month 3 in the JEOc
•To evaluate the VRR to the HZ/su candidate vaccine in the SC-vaccinated subjects ≥50 YOA at Month 3
–based on HI response in the Japanese ethnic origin cohort (JEOc).
–based on cell-mediated immune (CMI) response in the entire and the JEOc CMI subcohorts
•To evaluate HI & CMI responses to the HZ/su candidate vaccine administered by SC injection to subjects ≥50 YOA from Month 0 to Month 14
–in all subjects and in the JEOc
–in all subjects and in the JEOc subjects of the CMI subcohort, respectively
•To evaluate safety and reactogenicity of the HZ/su candidate vaccine when administered by SC injection to subjects ≥50 YOA up to Month 3 in the JEOc
•To evaluate safety of the HZ/su candidate vaccine when administered by SC injection to subjects ≥50 YOA from Month 3 through Month 14 in all subjects and in the JEOc

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A study to detect and characterise early/innate immune responses of GSK Biologicals’ Herpes Zoster subunit (HZ/su) vaccine GSK1437173A when administered subcutaneously vs. intramuscularly in adults aged ≥50 years

E.3

Principal inclusion criteria

•Subject who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
•Subject, if residing in Japan, is of Japanese ethnic origin, defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese.
•Subject, if not residing in Japan, may be of any ethnic origin.
•Subject has provided written informed consent.
•Subject, male or female, who is 50 YOA or older at the time of the first vaccination.
•Subject, if female, of non-childbearing potential may be enrolled in the study.
-Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
•Subject, if female, of childbearing potential may be enrolled in the 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 (i.e., for 2 months after Month 2).

E.4

Principal exclusion criteria

•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Concurrently participating or planned participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
•Administration or planned administration of a live vaccine within 30 days prior to the first study vaccination through 30 days after the second study vaccination.
•Administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
•Planned administration, during the study, of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
•Administration of immunoglobulins and/or any blood products within the three (3) months preceding the first dose of study vaccine or planned administration during the study period.
•Chronic administration (defined as > 14 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
-For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, is allowed.
-Inhaled, topical, and intra-articular corticosteroids are allowed.
•Administration or planned administration of long-acting immune-modifying drugs (e.g., infliximab) within six months prior to the first vaccine dose through the duration of the study period.
•History of HZ.
•Previous vaccination against HZ or varicella (registered or investigational product).
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.
•Significant underlying illness that, in the opinion of the investigator, would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 1 year).
•Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
•Acute disease and/or fever at the time of vaccination:
-Fever is defined as temperature ≥ 37.5°C (99.5°F) for oral, axillary, or tympanic route, or ≥ 38.0°C/100.4°F for rectal route. The preferred route for recording temperature in this study will be oral.
-Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
•Pregnant or lactating female.
•Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) through Month 4 (i.e., 2 months after the second dose of study vaccine).

E.5 End points

E.5.1

Primary end point(s)

A. Evaluation of gE-specific antibody concentrations.
–Anti-gE antibody concentration as determined by enzyme-linked immunosorbent assay (ELISA)
–Vaccine response, based on anti-gE humoral immune response as determined by ELISA
B. Occurrence of solicited local and general symptoms.
–Occurrence, intensity, and duration of each solicited local symptom
–Occurrence, intensity, duration, and relationship to vaccination of each solicited general symptom
C. Occurrence of unsolicited symptoms.
–Occurrence, intensity, and relationship to vaccination of each unsolicited symptom according to the Medical Dictionary for Regulatory Activities (MedDRA) classification
D. Occurrence of serious adverse events (SAEs).
–Occurrence, and relationship to vaccination of all SAEs
E. Occurrence of adverse events (AEs) of specific interest [Potential Immune-Mediated Disease (pIMDs)].
–Occurrence of any pIMDs

E.5.1.1

Timepoint(s) of evaluation of this end point

–At Month 3 (for A.).
–Within 7 days (Days 0-6) after each vaccination (for B.)
–Within 30 days (Days 0-29) after each vaccination (for C.)
–From Month 0 (vaccination 1) up to Month 3 (30 days post-vaccination 2) (for D. and E.)

E.5.2

Secondary end point(s)

A. Evaluation of gE-specific antibody concentrations.
–Anti-gE antibody concentrations as determined by ELISA.
Evaluated in all subjects and for each cohort: Japanese and Non Japanese ethnic origin cohorts (JEOc and NJEOc).
B. Evaluation of gE-specific antibody concentrations.
–Vaccine response, based on anti-gE humoral immune response as determined by ELISA.
Evaluated in all subjects and for each cohort:JEOc and NJEOc.
C. Evaluation of gE-specific CD4+ T-cell mediated immunogenicity.
–For subjects in the CMI subcohort, frequencies of gE-specific CD4+ T-cells responses expressing at least 2 activation markers (from among interferon gamma [IFN-γ], interleukin-2 [IL-2], tumour necrosis factor alpha [TNF-α], and CD40L), as determined by in vitro intracellular cytokine staining (ICS).
Evaluated in the entire CMI subcohort and in the portion of the CMI subcohort within the JEOc and NJEOc.
D. Evaluation of gE-specific CD4+ T-cell mediated immunogenicity.
–For subjects in the CMI subcohort, vaccine response for gE-specific CD4+ T-cells expressing at least 2 activation markers (from among IFN-γ, IL-2, TNF-α, and CD40L), as determined by in vitro ICS.
Evaluated in the entire CMI subcohort and in the portion of the CMI subcohort within the JEOc and NJEOc.
E. Occurrence of solicited local and general symptoms.
–Occurrence, intensity, and duration of each solicited local symptom.
–Occurrence, intensity, duration, and relationship to vaccination of each solicited general symptom.
Evaluated for each cohort: JEOc and NJEOc.
F. Occurrence of unsolicited symptoms (AEs).
–Occurrence, intensity, and relationship to vaccination of each unsolicited symptom.
Evaluated for each cohort: JEOc and NJEOc.
G. Occurrence of Serious Adverse Events (SAEs).
–Occurrence and relationship to vaccination of all SAEs.
Evaluated for each cohort: JEOc and NJEOc.
H. Occurrence of AEs of specific interest (pIMDs).
–Occurrence of any pIMDs.
Evaluated for each cohort: JEOc and NJEOc.
I. Occurrence of Serious Adverse Events (SAEs).
–Occurrence and relationship to vaccination of all SAEs.
Evaluated for all subjects and each cohort: JEOc and NJEOc.
J. Occurrence of AEs of specific interest (pIMDs).
–Occurrence of any pIMDs.
Evaluated for all subjects and each cohort: JEOc and NJEOc.

E.5.2.1

Timepoint(s) of evaluation of this end point

–At Months 0, 2, 3 and 14 (for A.)
–At Months 2, 3 and 14 (for B.)
–At Months 0, 3 and 14 (for C.)
–At Months 3 and 14 (for D.)
–Within 7 days (Days 0-6) after each vaccination (for E.)
–Within 30 days (Days 0-29) after each vaccination (for F.)
–From Month 0 (vaccination 1) up to Month 3 (30 days post-vaccination 2) (for G. and H.)
–From Month 3 (30 days post-vaccination 2) up to Month 14 (12 months post-vaccination 2) (for I. and J.)

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

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

Immunogenicity, Prevention

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

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

Different routes of administration (IM versus SC) of the HZ/su vaccine will be the comparator

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

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

Japan

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

LSLV

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:

650

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

432

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

682

F.4.2

For a multinational trial

F.4.2.1

In the EEA

682

F.4.2.2

In the whole clinical trial

1082

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)

None

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

2013-09-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-11

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