Clinical Trials Register

Summary
EudraCT Number:	2015-000965-30
Sponsor's Protocol Code Number:	204486
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-28
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

Spain - AEMPS

A.2

EudraCT number

2015-000965-30

A.3

Full title of the trial

A Phase IIIB, non-randomized, open-label, multi-country, multi-centric cross-vaccination study to evaluate the safety of GSK Biologicals' Herpes Zoster subunit (HZ/su) vaccine when administered intramuscularly on a two-dose schedule to subjects who previously received placebo in ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) studies.

Estudio fase IIIB, no aleatorizado, abierto, multinacional, multicéntrico de vacunación cruzada para evaluar la seguridad de la vacuna de subunidades frente al Herpes Zóster (HZ/su) de GSK Biologicals cuando se administra por vía intramuscular conforme a una pauta de 2 dosis a sujetos que previamente recibieron placebo en los estudios ZOSTER-006 y ZOSTER-022.

A.3.1

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

Cross-vaccination study of GSK Biologicals? Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A) in subjects who previously received placebo in ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) studies.

Estudio de vacunación cruzada con la formulación liofilizada de la vacuna de subunidades frente al Herpes Zóster (HZ/su) de GSK Biologicals (GSK 1437173A) en sujetos que previamente recibieron placebo en los estudios ZOSTER-006 y ZOSTER-022.

A.3.2

Name or abbreviated title of the trial where available

Zoster-056

A.4.1

Sponsor's protocol code number

204486

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 S.A.
B.1.3.4	Country	Spain
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
B.5.2	Functional name of contact point	Centro de Información
B.5.3	Address:
B.5.3.1	Street Address	C/Severo Ochoa, 2 (P.T.M.)
B.5.3.2	Town/ city	Tres Cantos (Madrid)
B.5.3.3	Post code	28760
B.5.3.4	Country	Spain
B.5.4	Telephone number	34902202700
B.5.5	Fax number	34918070479
B.5.6	E-mail	es-ci@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	Vacuna frente al Herpes Zoster (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	GLUCOPROTEÍNA E RECOMBINANTE DE SUPERFICIE DEL VIRUS DE LA VARICELA ZÓTER
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

Herpes Zoster

Herpes Zóster

E.1.1.1

Medical condition in easily understood language

Herpes zoster (Shingles) disease.

Enfermedad Herpes Zóster (culebrilla)

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	19.1
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 evaluate the safety, in terms of unsolicited adverse events (AE), Serious Adverse Events (SAE) and potential Immune Mediated Disease (pIMD) in all subjects, following administration of each dose of the HZ/su vaccine.

Evaluar la seguridad en lo que se refiere a acontecimientos adversos (AA) no solicitados, acontecimientos adversos graves (AAG) y enfermedad potencialmente mediada por el sistema inmune (pIMD) en todos los sujetos, tras la administración de cada dosis de la vacuna HZ/su.

E.2.2

Secondary objectives of the trial

To evaluate the incidence of suspected HZ episodes (self-reported or medically diagnosed) during the entire study period.

Evaluar la incidencia de episodios sospechosos de HZ (comunicados por el sujeto o diagnosticados médicamente) durante todo el período de estudio.

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, vaccination visits, follow-up contacts). Or subjects? Legally Acceptable Representative(s) [LAR(s)]/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, vaccination visits, availability for follow-up contacts).
? Written informed consent obtained from the subject/LAR(s) of the subject prior to performing any study specific procedure. If the subjects is not capable of giving consent, his/her assent to participate should be obtained to the extent possible.
? Subject who previously participated in ZOSTER-006 or ZOSTER-022 studies and received at least one dose of placebo.
? Female subjects 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.
? Female subjects of childbearing potential may be en-rolled 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.
*treatment period refers to vaccination days and the interval between them.

?Sujetos que, en opinión del investigador, puedan y vayan a cumplir los requisitos del protocolo (p. ej., cumplimentación de las tarjetas diario, visitas de vacunación, contactos de seguimiento). O representante legal [RL]/cuidador del sujeto que, en opinión del investigador, pueda y vaya a cumplir los requisitos del protocolo (por ejemplo, cumplimentación de las tarjetas diario, visitas de vacunación, disponibilidad para los contactos de seguimiento).
?Consentimiento informado por escrito obtenido del sujeto/RL del sujeto antes de realizar ningún procedimiento específico del estudio. Si el sujeto no es capaz de otorgar su consentimiento, deberá obtenerse su asentimiento en la medida de lo posible.
?Sujetos que participaron previamente en los estudios ZOSTER 006 o ZOSTER 002 y que recibieron al menos una dosis de placebo.
?Las mujeres sin capacidad reproductiva pueden incluirse en el estudio;
-Se consideran sin capacidad reproductiva las mujeres con premenarquia, ligadura de trompas actual, histerectomía, ovariectomía o posmenopausia;
?Las mujeres en edad fértil pueden incluirse en el estudio si:
-han utilizado un método anticonceptivo adecuado desde 30 días antes de la vacunación y
-tienen una prueba de embarazo negativa el día de la vacunación y
-han aceptado seguir utilizando un método anticonceptivo adecuado durante todo el período de tratamiento* y hasta 2 meses después de la finalización de la serie de vacunación.
*El período de tratamiento se refiere a los días de vacunación y al intervalo entre ellos.

E.4

Principal exclusion criteria

?Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 0), or planned use up to 30 days post Dose 2.
? Previous vaccination against VZV or HZ.
? Planned administration of VZV or HZ vaccination during the study (including an investigational or non-registered vaccine), with the exception of the study vaccine.
? Planned administration/administration of a vaccine/product not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of licensed non-replicating vaccines (i.e. inactivated and subunit vaccines, including inactivated and subunit influenza vaccines, with or without adjuvant for seasonal or pandemic flus). These may be administered up to 8 days prior to dose 1 and/or dose 2 and/or at least 14 days after any dose of study vaccine.
? Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose and up to 30 days post Dose 2. For corticosteroids, this will mean prednisone ? 20 mg/day or equivalent. Inhaled, topical and intra-articular corticosteroids are allowed.
? Administration of long-acting immune-modifying drugs (e.g. infliximab, rituximab) within six months prior to the first vaccine dose up to 30 days post Dose 2.
? Concurrently participating in another clinical study, at the time of enrolment or planned participation up to the 30 days post second dose, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
? 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).
? History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
? Active HZ infection at the time of enrolment (i.e. HZ lesions not completely crusted over).
? Pregnant or lactating female.
? Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
? Any condition which in the judgment of the investigator would make intramuscular injection unsafe.

?Uso de cualquier producto (fármaco o vacuna) en investigación o no registrado distinto de la vacuna del estudio desde 30 días antes de la administración de la primera dosis de la vacuna del estudio (día -29 a día 0) o uso previsto hasta 30 días después de la segunda dosis.
?Vacunación previa frente a VZV o HZ.
?Administración prevista de vacunas frente a VZV o HZ durante el estudio (incluida una vacuna en investigación o no registrada), a excepción de la vacuna del estudio.
?Administración confirmada o planeada de una vacuna no prevista por el protocolo del estudio desde 30 días antes de la administración de la primera dosis de vacuna hasta 30 días después de la administración de la última dosis de la vacuna, con la excepción de vacunas sin capacidad de replicación autorizadas (es decir, vacunas inactivadas y de subunidades, incluidas vacunas antigripales, con o sin adyuvante para la gripe estacional o pandémica). Estas vacunas pueden administrarse hasta 8 días antes de la dosis 1 y/o la dosis 2 y/o a partir de 14 días después de administrar cualquiera de las dosis de la vacuna del estudio.
?Administración crónica (definida como más de 14 días en total) de inmunodepresores u otros fármacos inmunomoduladores desde 6 meses antes de la primera dosis de la vacuna hasta 30 días después de la administración de la segunda dosis. En el caso de los corticosteroides, eso significará una dosis de prednisona ? de 20 mg/día o equivalente. Se permiten los corticosteroides inhalados, tópicos e intraarticulares.
?Administración de fármacos inmunomodulares de efecto prolongado (p. ej., infliximab, rituximab) desde seis meses antes de la primera dosis de la vacuna hasta 30 días después de la segunda dosis.
?La participación simultánea en otro estudio clínico, en el momento del reclutamiento o participación prevista hasta 30 días después de la segunda dosis, en el que el sujeto haya estado o vaya a estar expuesto a una vacuna o producto (producto farmacéutico o dispositivo) en investigación o no en investigación.
?Cualquier confirmación o sospecha de un estado de inmunosupresión o inmunodeficiencia como consecuencia de una enfermedad (p. ej., neoplasia maligna, infección por el virus de la inmunodeficiencia humana [VIH]) o tratamiento inmunosupresor/citotóxico (p. ej., medicamentos utilizados para quimioterapia en el cáncer, trasplante de órganos o tratamiento de trastornos autoinmunitarios).
?Antecedentes de cualquier reacción o hipersensibilidad que probablemente pueda exacerbarse por alguno de los componentes de la vacuna.
?Infección activa por HZ en el momento del reclutamiento (esto es, lesiones por HZ todavía con costra).
?Mujer en estado de gestación o lactancia.
?Cualquier condición que, en opinión del investigador, impida la participación del sujeto en el estudio.
?Cualquier condición que, en opinión del investigador, haría insegura la inyección intramuscular.

E.5 End points

E.5.1

Primary end point(s)

1. Occurrence, intensity and relationship to vaccination of unsolicited AEs according to the Medical Dictionary for Regulatory Activities (MedDRA) classification in all subjects
- 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

2. Occurrence and relationship to vaccination of all SAEs
- Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related = SAE assessed by the investigator as related to the vaccination.

3. Occurrence and relationship to vaccination of any pIMDs
- 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.

1. Aparición, intensidad y relación con la vacunación de acontecimientos adversos (AA) no solicitados, según la clasificación del Diccionario Médico de Actividades de Registro (MedDRA) en todos los sujetos.
-Un AA es toda experiencia médica no deseada que presente un sujeto sometido a investigación clínica asociado temporalmente al uso de un medicamento, se considere o no relacionado con él. Se define como la aparición de cualquier AA no solicitado con independencia del grado de intensidad o relación con la vacunación. AA Grado 3= un AA que impide las actividades cotidianas normales. Relacionado= AA valorado por el investigador como relacionado con la vacunación.
2. Aparición y relación con la vacunación de todos los Acontecimientos Adversos Graves (AAG).
-Un AAG es toda experiencia médica no deseada que causa la muerte, pone en peligro la vida, requiera hospitalización o prolonga una hospitalización, causa discapacidad o incapacidad. Relacionado= AAG valorado por el investigador como relacionado con la vacunación.
3. Aparición y relación con la vacunación de cualquier enfermedad potencialmente mediada por el sistema inmune (pIMDs).
- Las pIMDs son un subgrupo de AA que comprenden enfermedades autoinmunes y/o otros trastornos inflamatorios o neurológicos de interés que pueden o no tener una etiología autoinmunitaria.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. During 30 days (Days 0-29) after each vaccination.
2 and 3. From Month 0 until study end at 14 months.

1. Durante 30 días (días 0-29) después de cada vacunación.
2 y 3. Desde el mes 0 hasta el final del estudio a los 14 meses.

E.5.2

Secondary end point(s)

Ocurrence of suspected HZ cases from Month 0 to study end.

Aparición de casos sospechosos de HZ desde el mes 0 hasta el final del estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

From Month 0 until study end at 14 months

Desde el mes 0 hasta el final del estudio a los 14 meses.

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

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

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

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

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

110

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

LVLS

Última visita del último sujeto

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:

4758

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

9792

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Elderly subjects with impaired mental capacity, for whom a legally acceptable representative would sign to consent to study participation

Sujetos ancianos con capacidad mental deteriorada, para quienes un representante legal aceptable firmaría para consentir su participación en el estudio.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

852

F.4.2

For a multinational trial

F.4.2.1

In the EEA

7862

F.4.2.2

In the whole clinical trial

14550

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

Ninguno

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

2016-04-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-03-15

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