Clinical Trials Register

Summary
EudraCT Number:	2018-002977-24
Sponsor's Protocol Code Number:	209538
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:	2021-01-29
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

2018-002977-24

A.3

Full title of the trial

A Phase IIA, open-label study to evaluate the immunogenicity and safety of sequential use of GSK’s investigational vaccine GSK3277511A when administered to healthy smokers and ex-smokers aged 50 to 80 years following receipt of Shingrix vaccine.

Studio di fase IIA, in aperto per valutare immunogenicità e sicurezza della somministrazione sequenziale del vaccino sperimentale di GSK GSK3277511A quando somministrato a fumatori ed ex-fumatori d’età compresa tra 50 e 80 anni dopo aver ricevuto il vaccino Shingrix.

A.3.1

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

Study to assess the immunogenicity and safety of GSK's investigational vaccine (GSK3277511A) when given to healthy smokers and ex-smokers after Shingrix vaccination.

Studio per valutare l'immunogenicità e la sicurezza del vaccino sperimentale di GSK (GSK3277511A) quando somministrato a fumatori sani ed ex-fumatori dopo la vaccinazione Shingrix.

A.3.2

Name or abbreviated title of the trial where available

NTHI MCAT-009

A.4.1

Sponsor's protocol code number

209538

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	000000
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	Non-Typeable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) investigational vaccine
D.3.2	Product code	[NTHi-Mcat]
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	non-typeable Haemophilus influenzae PD
D.3.9.2	Current sponsor code	PD
D.3.9.3	Other descriptive name	Recombinant Non-typeable Haemophilus influenzae Protein D (PD)
D.3.9.4	EV Substance Code	SUB195012
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	non-typeable Haemophilus influenzae PE-PilA
D.3.9.2	Current sponsor code	PE-PilA
D.3.9.3	Other descriptive name	Recombinant Non-typeable Haemophilus influenzae PE and PilA fusion protein
D.3.9.4	EV Substance Code	SUB195013
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Moraxella catarrhalis UspA2
D.3.9.2	Current sponsor code	UspA2
D.3.9.3	Other descriptive name	Ubiquitous Surface Protein A2 (UspA2) from Moraxella catarrhalis.
D.3.9.4	EV Substance Code	SUB195014
D.3.10	Strength
D.3.10.1	Concentration unit	ng nanogram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3300
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Shingrix
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo SmithKline Biologicals S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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 subunit (HZ/su) vaccine (GSK1437173A)
D.3.2	Product code	[-]
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Varicella Zoster Virus glycoprotein E antigen
D.3.9.2	Current sponsor code	gE Antigen
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

Healthy volunteers (chronic obstructive pulmonary disorder [COPD])

Volontari sani (Broncopneumopatia Cronica Ostruttiva [BPCO])

E.1.1.1

Medical condition in easily understood language

COPD is a lung disease that makes it hard to breathe. It is caused by damage to the lungs over many years, usually from smoking.

La BPCO è una malattia dei polmoni che rende la respirazione difficoltosa. E' un danno ai polmoni, che di solito è causato dall'esposizione al fumo per molti anni.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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 the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 or 3 or 6 months after Shingrix vaccine versus the humoral im-mune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine alone.
A modified primary objective will be applicable if the sample size for the per-protocol set is not reached for the Sh_NTHi-Mcat_6 or the Sh_NTHi-
Mcat_6 and _3 groups. If the per protocol defined sample size is not reached for the Sh_NTHi-Mcat_6 and _3 groups, the NI testing will be performed on the Sh-NTHI-Mcat_1 group.

Criterion: NI will be demonstrated if the lower limit (LL) of the 2-sided 95% confidence interval (CI) of the geometric mean concentration (GMC) ratio (Sh_NTHi-Mcat/NTHi-Mcat) is above a limit of 0.667 for all anti-PD, anti-Protein E (PE), anti-type IV pili subunit (PilA), anti- ubiquitous surface protein A2 of Moraxella catarrhalis (Us-pA2).

Dimostrare la non inferiorità (NI) della risposta immunitaria umorale 1 mese dopo la Dose 2 del vaccino sperimentale di GSK Biologicals NTHi-Mcat quando somministrato 1 o 3 o 6 mesi dopo il vaccino Shingrix vs la risposta immunitaria umorale 1 mese dopo la Dose 2 del vaccino sperimentale di GSK Biologicals NTHi-Mcat quando somministrato da solo.
Un obiettivo primario modificato sarà applicabile se il dimensionamento campionario per la popolazione “per-protocol” non sarà raggiunto per il gruppo Sh_NTHi-Mcat_6 o i gruppi Sh_NTHi- Mcat_6 e _3. Se il dimensionamento campionario “per-protocol” definito non sarà raggiunto per i gruppi Sh_NTHi- Mcat_6 e _3 il test di NI sarà effettuato sul gruppo Sh-NTHI-Mcat_1.

Criterio: Limite Inferiore (LL) dell’intervallo di confidenza (IC) bilaterale al 95% del rapporto tra le medie geometriche delle concentrazioni (Sh_NTHi-Mcat/NTHi-Mcat) (95%) maggiore di 0.667 per tutti gli anticorpi anti-PD, anti-PE, anti-PilA e anti-UspA2.

E.2.2

Secondary objectives of the trial

• To evaluate the safety and reactogenicity profile of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 or 3 or 6 months after Shingrix vaccine or when administered alone.
• To describe the humoral immune response of GSK Biologicals' NTHi- Mcat investigational vaccine when administered 1 or 3 or 6 months after Shingrix vaccine or when administered alone.
• To describe the cell-mediated immune (CMI) response of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 or 3
or 6 months after Shingrix vaccine or when NTHi-Mcat is administered alone, in the CMI response subcohort.

• Valutare il profilo di sicurezza e reattogenicità del vaccino sperimentale di GSK Biologicals NTHi-Mcat quando somministrato 1 o 3 o 6 mesi dopo il vaccino Shingrix o quando somministrato da solo.
• Descrivere la risposta immunitaria umorale del vaccino sperimentale di GSK Biologicals NTHi-Mcat quando somministrato 1 o 3 o 6 mesi dopo il vaccino Shingrix o quando somministrato da solo.
• Descrivere la risposta (cellule T CD4+) immunitaria cellulo-mediata (CMI) del vaccino sperimentale di GSK Biologicals NTHi-Mcat quando somministrato 1 o 3 o 6 mesi dopo il vaccino Shingrix o quando somministrato da solo, nella sub-coorte CMI.

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).
• Written informed consent obtained from the subject prior to performance of any study specific procedure.
• A male or female between, and including, 50 years and 80 years of age at the time of the first vaccination.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Current or former smoker with a cigarette smoking history =10 packyears.
• Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlu-sion, hysterectomy, bilateral ovariectomy or post-menopause.
• Female subjects 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.

• Soggetti che secondo il giudizio dello Sperimentatore, possono rispettare e rispetteranno le richieste del protocollo (per es. compilazione scheda diario elettronica, ritornare per le visite di follow-up).
• Ottenimento consenso informato scritto dal soggetto prima di effettuare qualsiasi procedura dello studio.
• Soggetto di sesso maschile o femminile, d’età compresa tra 50 e 80 anni al momento della prima vaccinazione.
• Soggetti sani, come stabilito dalla storia medica e dall’esame clinico prima di entrare nello studio.
• Fumatore attivo o ex fumatore con un’anamnesi di fumo di sigaretta =10 pacchetti-anno.
• Donne non potenzialmente fertili possono essere arruolate nello studio. Soggetto potenzialmente non fertile è definito come pre-menarca, attuale legatura bilaterale delle tube o occlusione tubarica, ovariectomia bilaterale o post-menopausa.
• Donne potenzialmente fertili possono essere arruolate nello studio, se il soggetto (fare riferimento alla Sezione 12.6.1 per la definizione di donne potenzialmente fertili): ha utilizzato un metodo contraccettivo adeguato per 30 giorni prima della vaccinazione (fare riferimento alla Sezione 12.6.2 per la definizione di metodo contraccettivo adeguato), e ha un test di gravidanza sulle urine negativo il giorno della vaccinazione, ed è d’accordo a continuare un‘adeguata contraccezione durante il periodo di trattamento e per 2 mesi dopo la conclusione della serie di vaccinazioni.

E.4

Principal exclusion criteria

Medical conditions:
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of potential immune-mediated disease (pIMD).
Note: If the subject has any condition on the list of pIMDs specified in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated. The investigator will exercise his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin and thus meet the exclusion criteria.
• Diagnosis of COPD regardless of severity.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Additionally, consider allergic reactions to other material or equipment related to study participation (such as materials that may possibly contain latex –gloves, syringes, etc).
• Has significant disease (including significant psychological disorders), in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration.
• History of or current condition preventing intramuscular injection as bleeding or coagulation disorder.
• Malignancies within previous 5 years (excluding non-melanoma skin cancer) or lymphoproliferative disorders.

Prior/concomitant therapy:
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period.
• Planned administration/administration of a vaccine 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 non-MF59 adjuvanted influenza vaccines and pneumococcal vaccines which may be administered =15 days preceding or following any study vaccine dose.
Note: For M59 adjuvanted flu vaccine and for any vaccine containing novel adjuvant refer to exclusion criteria below.
• Planned administration/administration of a vaccine adjuvanted with the following adjuvants AS01, AS02, AS03, AS04 and MF59 in the period starting 6 months before the first dose of study vaccine, and ending at the second blood draw (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). The following nonexhaustive list should be considered as criteria for exclusion: Prepandrix, Adjupanrix, Shingrix, Fendrix, Cervarix, FluAd, Chiromas, Gripguard.
• Previous vaccination with any vaccine containing NTHi and/or Mcat antigens;
• Previous vaccination with Shingrix; (either registered product or participation in a previous vaccine study).
• Previous vaccination with HZ live-attenuated vaccine (ZVL)) (either registered product or participation in a previous vaccine study) within the 2 months of the first study visit (Day 1).
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose, and ending at the second blood draw. (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). For corticosteroids, this will mean prednisone =5 mg/day (for adult subjects), or equivalent. Only topical steroids are allowed.
For further exclusion criteria please refer to the protocol.

Condizioni mediche:
• Qualsiasi condizione immunosoppressiva o immunodeficiente confermata o sospetta, sulla base della storia medica e dell’esame fisico (non sono richiesti esami di laboratorio).
• Storia di potenziale malattia immuno-mediata (pIMD).
Nota: Fare riferimento alla Tabella 23 (pag. 95-96 del protocollo) per un elenco non esaustivo, delle potenziali malattie immuno-mediate. Se il soggetto presenta una qualsiasi condizione presente in questa elenco, deve essere escluso, a meno che non sia chiaramente documentato che l’eziologia non è immuno-mediata.
Lo Sperimentatore eserciterà il suo giudizio medico e scientifico per decidere se le altre malattie hanno un’origine autoimmune e quindi soddisfano il criterio di esclusione.
• Diagnosi di BPCO indipendentemente dalla gravità.
• Storia di qualsiasi reazione o ipersensibilità potenzialmente aggravata da qualsiasi componente dei vaccini. Inoltre, vanno considerate le reazioni allergiche a altri materiali o dispositivi medici correlati alla partecipazione allo studio (come materiali che potrebbero contenere latex – guanti, siringhe, etc).
• Patologia (inclusi disturbi mentali significativi), che secondo l’opinione dello Sperimentatore potrebbe interferire con lo studio e/o potrebbe causare il decesso durante il periodo dello studio.
• Storia di o una condizione attuale che impedisce la somministrazione intramuscolare come sanguinamento o disturbo della coagulazione.
• Patologia tumorale maligna nei 5 anni precedenti (eccetto carcinoma cutaneo non melanomatoso) o disordini linfoproliferativi.

Terapia precedente/concomitante:
• Uso di prodotti sperimentali o non registrati (farmaco o vaccino), ad eccezione del vaccino in studio, nei 30 giorni prima della prima dose del vaccino dello studio (Giorno -29 a Giorno 1), o previsione di utilizzo di tali prodotti durante lo studio.
• Pianificazione/ somministrazione di un vaccino non previsto dallo studio nel periodo compreso fra i 30 giorni precedenti la prima dose e i 30 successivi dopo l’ultima somministrazione del vaccino in studio, ad eccezione dei vaccini antinfluenzali non adiuvati con MF59 e lo pneumococco che potranno essere somministrati =15 giorni prima o dopo ogni dose di vaccino dello studio.
Nota: per il vaccino antinfluenzale adiuvato con MF59 e per qualsiasi vaccino contente un nuovo adiuvante fare riferimento al seguente criterio di esclusione.
• Somministrazione pianificata di un vaccino adiuvato con i seguenti adiuvanti AS01, AS02, AS03, AS04 e MF59 nel periodo che inizia 6 mesi prima della prima dose del vaccino dello studio e che termina al secondo prelievo di sangue (cioè circa 1 mese dopo l’ultima somministrazione del vaccino NTHi-Mcat). La seguente lista non esaustiva deve essere considerata un criterio di esclusione: Prepandrix, Adjupanrix, Shingrix, Fendrix, Cervarix, FluAd, Chiromas, Gripguard.
• Precedente vaccinazione con qualsiasi vaccino contenente gli antigeni NTHi e/o Mcat.
• Precedente vaccinazione con Shingrix, (sia il prodotto registrato sia la partecipazione in un precedente studio con il vaccino).
• Precedente vaccinazione con il vaccino HZ vivo-attenuato (ZVL) (sia il prodotto registrato sia la partecipazione in un precedente studio con il vaccino) entro 2 mesi dalla prima visita dello studio (Giorno 1).
• Somministrazione di farmaci immunomodulatori a lunga durata in qualsiasi momento durante il periodo di studio (per esempio infliximab).
• Somministrazione cronica (definita come superiore a 14 giorni in totale) di farmaci immunosoppressori o immunomodulatori durante il periodo che inizia 6 mesi prima della prima dose del vaccino dello studio e che termina al secondo prelievo di sangue (cioè circa 1 mese dopo l’ultima somministrazione del vaccino NTHi-Mcat). Per i corticosteroidi, significherà prednisone = 5 mg/giorno o equivalente (per soggetti adulti). Sono permessi solo steroidi topici.
Per ulteriori criteri di esclusione si prega di far riferimento alla sinossi del protocollo.

E.5 End points

E.5.1

Primary end point(s)

Anti-PD, anti-PE, anti-PilA and anti-UspA2 antibody concentrations in terms of Geometric Mean Concentrations (GMCs), one-month post Dose-
2 of NTHi-Mcat vaccine.

Antibody concentrations are measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153, 25 ,16 and 38 EU/mL for anti-PD, anti-PE, anti-PilA and anti-UspA2 antibodies respectively.
If per protocol set (PPS) sample size is not met in Sh_NTHi_Mcat_6 group then timeframe will be adapted as follows: At 1 month after Dose
2 of NTHi-Mcat vaccine (Day 181, 241 in Sh_NTHi-Mcat_1 and Sh_NTHi- Mcat_3 group respectively and Day 91 in NTHi-Mcat group)
If PPS sample size is not met in Sh_NTHi_Mcat_6 or in Sh_NTHi-Mcat_6 and Sh_NTHi-Mcat_3 groups then timeframe will be adapted as follows:
At 1 month after Dose 2 of NTHi-Mcat vaccine (Day 181 in Sh_NTHi- Mcat_1 group and Day 91 in NTHi-Mcat group).

Concentrazioni degli anticorpi Anti-PD, anti-PE, anti-PilA e anti-UspA2 in termini di Concentrazioni Medie Geometriche (Geometric Mean Concentrations - GMCs), un mese dopo la Dose 2 del vaccino NTHi-Mcat.

Le concentrazioni degli anticorpi sono misurate tramite ELISA (Enzyme-linked immunosorbent assay) ed espresse come GMCs in unità ELISA per millilitro (EU/mL). Il valore cut-off per il saggio è pari a 153, 25 ,16 e 38 EU/mL per gli anticorpi anti-PD, anti-PE, anti-PilA e anti-UspA2, rispettivamente.
Se il dimensionamento campionario per la popolazione “per-protocol” (Per-Protocol Set - PPS) non sarà raggiunto nel gruppo Sh_NTHi_Mcat_6 la tempistica sarà adattata come segue: 1 mese dopo la Dose 2 del vaccino NTHi-Mcat (Giorno 181 e 241 per i gruppi Sh_NTHi-Mcat_1 e Sh_NTHi- Mcat_3, rispettivamente, e Giorno 91 per il gruppo NTHi-Mcat).
Se il dimensionamento campionario per il PPS non sarà raggiunto nel gruppo Sh_NTHi_Mcat_6 o nei gruppi Sh_NTHi-Mcat_6 e Sh_NTHi-Mcat_3 la tempistica sarà adattata come segue: 1 mese dopo la Dose 2 del vaccino NTHi-Mcat (Giorno 181 per il gruppo Sh_NTHi- Mcat_1 e Giorno 92 per il gruppo NTHi-Mcat).

E.5.1.1

Timepoint(s) of evaluation of this end point

At 1 month after Dose 2 of NTHi-Mcat vaccine (Day 181 [Sh_NTHi-Mcat_1], Day 241 [Sh_NTHi-Mcat_3] and Day 331 [Sh_NTHi-Mcat_6], and Day 91 [NTHi-Mcat]).

1 mese dopo la Dose 2 del vaccino NTHi-Mcat (Giorno 181 [Sh_NTHi-Mcat_1], Giorno 241 [Sh_NTHi-Mcat_3], Giorno 331 [Sh_NTHi-Mcat_6] e Giorno 91 [NTHi-Mcat]).

E.5.2

Secondary end point(s)

Occurrence of each solicited local and general adverse event (AE), reported in all subjects in all groups.; Occurrence of any unsolicited AEs, reported in all subjects in all groups.; Serious AEs:
1. Occurrence of any SAE reported in all subjects in all groups.
2. Occurrence of any SAE, reported in all subjects in all groups.
3. Potential immune-mediate diseases (pIMD)
4. Occurrence of any pIMD, reported in all subjects in all groups.
5. Occurrence of any pIMD, reported in all subjects in all groups.; Anti-PD, anti-PE, anti-PilA and anti-UspA2 antibody concentrations and seropositivity in all subjects.; NTHi-specific and Mcat-specific CMI responses as measured by flow cytometry ICS (frequency of specific CD4+ T-cells expressing at least 2 different markers among CD40 ligand (CD40L), interleukin (IL)-2, IL-13, IL-17, interferon gamma (IFN-¿), tumour necrosis factor alpha (TNF-a) upon in vitro stimulation).

Incidenza di ciascun evento locale e generale (AE) atteso, riportato in tutti i soggetti e in tutti i gruppi.; Incidenza di qualsiasi AE non atteso riportato in tutti i soggetti e in tutti i gruppi.; AE gravi:
1. Incidenza di qualsiasi SAE riportato in tutti i soggetti e in tutti i gruppi.
2. Incidenza di qualsiasi SAE riportato in tutti i soggetti e in tutti i gruppi.
3. Potenziali malattie immuno-mediate (pIMD).
4. Incidenza di qualsiasi pIMD, riportata in tutti i soggetti e in tutti i gruppi.
5. Incidenza di qualsiasi pIMD, in tutti i soggetti e in tutti i gruppi.; Concentrazione e sieropositività degli anticorpi anti-PD, anti-PE, anti-PilA e anti-UspA2 in tutti i soggetti.; Risposta immunitaria cellulo-mediata NTHi- e Mcat-specifica misurata con citometria a flusso ICS (frequenza di specifiche cellule T CD4+ che esprimono almeno due diversi marcatori tra il legando CD40 (CD40L), l’interleuchina IL-2, IL-13, IL-17, interferone gamma (IFN-¿), fattore di necrosi tumorale alfa (TNF-a) dopo stimolazione in vitro).

E.5.2.1

Timepoint(s) of evaluation of this end point

During a 7-day follow- up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine.; During a 30-day follow- up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine.; 1. From first vaccination (Day 1) to Day 331.
2. From Day 331 to Day 661.
3. During the study.
4. From first vaccination (Day 1) to Day 331.
5. From Day 331 to Day 661.; Before Dose 1 (Day 91; Day 151; Day 241 in the Sh_NTHi-Mcat groups and Day 1 in the NTHi-Mcat group), and 1 month after Dose 2 of NTHi-Mcat vaccine (Day 181; Day 241; Day 331 in the Sh_NTHi-Mcat groups and Day 91 in the NTHi-Mcat group).; Before Dose 1 (Day 91; Day 151; Day 241 in the Sh_NTHi-

Durante un periodo di follow up di 7 giorni (cioè giorno della vaccinazione e i successivi 6 giorni), dopo la Dose 1 e dopo la Dose 2 del vaccino sperimentale di GSK Biologicals NTHi-Mcat.; Durante un periodo di follow-up di 30 giorni (cioè giorno della vaccinazione e i successivi 29 giorni), dopo la Dose 1 e dopo la Dose 2 del vaccino sperimentale di GSK Biologicals NTHi-Mcat.; 1. Dalla prima vaccinazione (Giorno 1) al Giorno 331.
2. Dal Giorno 331 al Giorno 661.
3. Durante lo studio.
4. Dalla prima vaccinazione (Giorno 1) al Giorno 331.
5. Dal Giorno 331 al Giorno 661.; Prima della Dose 1 (Giorno 91; Giorno 151; Giorno 241 nei gruppi Sh_NTHi-Mcat e Giorno 1 nel gruppo NTHi-Mcat) e 1 mese dopo la Dose 2 del vaccino NTHi-Mcat (Giorno 181; Giorno 241; Giorno 331 nei gruppi Sh_NTHi-Mcat e Gi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

Immunogenicità

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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)

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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 (Day 661)

LSLV (Giorno 661)

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:

360

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

540

F.4.2.2

In the whole clinical trial

540

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)

No plan for treatment or care after the subject has ended the participation in this trial is provided for prophylactic vaccine studies as the subjects are healthy and do not need any treatment or care after end of the study.

Non è previsto un piano di trattamento o cura dopo che il soggetto avrà concluso la partecipazione a questo studio, poiché i soggetti arruolati negli studi con vaccini profilattici sono sani.

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

2019-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-02-20

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

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Orphan Designation Number:
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