Clinical Trials Register

Summary
EudraCT Number:	2015-000965-30
Sponsor's Protocol Code Number:	204486
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

Italy - Italian Medicines Agency

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.

Studio clinico di fase IIIB, multi-paese, multicentrico, di cross-vaccinazione, non randomizzato, in aperto, volto a valutare la sicurezza del vaccino contro l’Herpes zoster (HZ/su) di GSK Biologicals, quando somministrato per via intramuscolare secondo una schedula a 2 dosi in soggetti precedentemente trattati con placebo negli studi ZOSTER-006 e ZOSTER-022. (Titolo completo della sperimentazione in inglese): 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 and ZOSTER-022 studies.

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.

Studio di cross-vaccinazione sul vaccino (GSK 1437173A) contro l'Herpes Zoster (HZ/su) di GSK Biologicals in soggetti che in precedenza hanno ricevuto il placebo negli studi ZOSTER-006 (NCT01165177) e ZOSTER-022 (NCT01165229).

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 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	00442089904466
B.5.5	Fax number	003210853710
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 solvent for solution 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.3.9.2	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

E.1.1.1

Medical condition in easily understood language

Herpes zoster (Shingles) disease.

Malattia Herpes Zoster (Fuoco di Sant'Antonio)

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 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.

Valutare la sicurezza, in termini di eventi avversi (AE) spontaneamente riportati, eventi avversi seri (SAE) e pIMD (malattie potenzialmente immuno-mediate) in tutti i soggetti, dopo la somministrazione di ciascuna dose di vaccino 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.

Valutare l’incidenza dei casi sospetti di HZ (auto segnalati o clinicamente diagnosticati) durante l’intera durata dello studio.

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.

• Soggetto che sia ritenuto dello sperimentatore, capace e desideroso di osservare quanto richiesto dal protocollo di studio (per esempio, compilazione delle schede diario, visite per le vaccinazioni, contatti durante il follow-up). Oppure rappresentante legale[LAR]/caregiver dei soggetti che, a parere dello sperimentatore, siano capaci e desiderosi di osservare quanto richiesto dal protocollo di studio (ossia, compilazione delle schede diario, visite per le vaccinazioni, disponibilità per i contatti durante il follow-up).
• Consenso informato scritto fornito dal soggetto/o dal legale rappresentante del soggetto ottenuto prima di eseguire qualsiasi procedura specifica dello studio. Se il soggetto non è in grado di fornire il consenso, il suo assenso a partecipare allo studio deve essere ottenuto nella misura del possibile.
• Soggetto che ha preso parte in precedenza agli studi ZOSTER-006 o ZOSTER-022 e che ha ricevuto almeno una dose di placebo.
• Donne non potenzialmente fertili possono essere arruolate nello studio.
¿ Per “non potenzialmente fertili” si intendono soggetti in età pre-menarca, sottoposti a legatura tubarica, isterectomia, ovariectomia o in post-menopausa.
• Donne potenzialmente fertili possono essere arruolate nello studio se:
¿ hanno utilizzato un metodo contraccettivo adeguato* da almeno 30 giorni prima della vaccinazione
¿ risultano negative al test di gravidanza eseguito il giorno stesso della vaccinazione, e
¿ hanno consentito ad adottare un metodo contraccettivo adeguato durante l’intero periodo di trattamento* e nei 2 mesi successivi al completamento del ciclo di vaccinazione.
*il periodo di trattamento si riferisce ai giorni di vaccinazione ed all'intervallo tra questi.

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.

• Utilizzo di un qualsiasi farmaco o vaccino sperimentale o non registrato, escluso il presente vaccino in studio, nei 30 giorni precedenti la prima dose del vaccino in studio (dal Giorno -29 al Giorno 0), o uso programmato nei 30 giorni successi alla dose 2.
• Precedente vaccinazione contro l’HZ o contro la varicella.
• Somministrazione di un vaccino anti-HZ o anti-varicella, anche sperimentale o non registrato, diverso dal vaccino in studio, programmata durante lo studio.
• Somministrazione programmata di un vaccino/prodotto non previsto dal protocollo di studio nei 30 giorni precedenti la prima dose del vaccino fino a 30 giorni dopo l’ultima dose di vaccino somministrata, ad eccezione dei vaccini non replicanti registrati (ossia, vaccini inattivati e a sub-unità, inclusi i vaccini antinfluenzali inattivati e a sub-unità, con o senza adiuvante per le influenze stagionali o pandemiche). Questi vaccini possono essere somministrati fino a 8 giorni prima della dose 1 e/o della dose 2 e/o almeno 14 giorni dopo una dose qualsiasi del vaccino dello studio.
• Somministrazione cronica (definita come maggiore di 14 giorni consecutivi) di farmaci immunosoppressori o di altri immuno-modulatori nei 6 mesi precedenti la prima dose di vaccino fino a 30 giorni dopo la dose 2 Per i corticosteroidi, si intende prednisone in dose = 20 mg/die o equivalente. Sono consentiti corticosteroidi per uso inalatorio topico e intra-articolare.
• Somministrazione di farmaci immuno-modulatori con azione a lunga durata (ad es. infliximab, rituximab) nei sei mesi precedenti la prima dose di vaccino, fino a 30 giorni dopo la dose 2.
• Partecipazione concomitante, al momento dell’arruolamento o programmata, ad un altro studio clinico in cui il soggetto è stato o verrà esposto ad un vaccino/prodotto sperimentale o non sperimentale (prodotto farmaceutico o dispositivo) fino a 30 giorni dopo la seconda dose.
• Qualsiasi condizione di immunodeficienza o di immunosoppressione, confermata o sospetta, derivante da patologie (ad es. neoplasia maligna, infezione da virus dell’immunodeficienza umana [HIV]) o da terapia immunosoppressiva/citotossica (ad es. farmaci utilizzati durante la chemioterapia oncologica, per i trapianti d’organo o per il trattamento di malattie autoimmuni).
• Storia di ipersensibilità o di reazioni allergiche che potrebbe essere aggravate da un qualsiasi componente del vaccino.
• Infezione da HZ attiva al momento dell’arruolamento (cioè lesioni da HZ le cui croste non sono completamente risolte).
• Donne in gravidanza o allattamento.
• Qualsiasi condizione che, a parere dello sperimentatore, impedisca al soggetto di prendere parte allo studio.
• Qualsiasi condizione che, a giudizio dello sperimentatore, potrebbe rendere l’iniezione intramuscolare non sicura.

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.

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.

E.5.2

Secondary end point(s)

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

E.5.2.1

Timepoint(s) of evaluation of this end point

From Month 0 until study end at 14 months

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

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

Studio in aperto

Open-label study

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

Information not present in EudraCT

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

Czechia

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

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

Soggetti anziani con ridotta capacità mentale, per i quali un legale rappresentante accettabile dovrebbe firmare per consentire la loro partecipazione allo studio

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

234

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

Nessuno

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

2016-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-19

P. End of Trial
P.	End of Trial Status	Completed

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