Clinical Trials Register

Summary
EudraCT Number:	2020-005273-27
Sponsor's Protocol Code Number:	VAC52416BAC3001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-06-21
Trial results

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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-005273-27

A.3

Full title of the trial

Randomized, Double-Blind, Placebo-controlled, Multicenter Phase 3 Study to Assess the Efficacy, Safety And Immunogenicity of Vaccination With ExPEC9V in the Prevention of Invasive Extraintestinal Pathogenic Escherichia coli Disease in Adults Aged 60 Years And Older with a History of Urinary Tract Infection in the Past 2 Years.

Studio multicentrico di fase 3, randomizzato, in doppio cieco, controllato con placebo per valutare l’efficacia, la sicurezza e l’immunogenicità della vaccinazione con ExPEC9V nella prevenzione della malattia invasiva da escherichia coli patogeno extraintestinale in adulti di età pari o superiore a 60 anni con anamnesi di infezione del tratto urinario negli ultimi 2 anni

A.3.1

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

A study to evaluate ExPEC9V vaccine for the prevention of Invasive E. coli Disease in adults aged 60 years and older with a history of urinary tract infection in the past two years.

Uno studio per valutare il vaccino ExPEC9V per la prevenzione della malattia invasiva da escherichia coli negli adulti di età pari o superiore a 60 anni con una storia di infezione del tratto urinario negli ultimi 2 anni.

A.3.2

Name or abbreviated title of the trial where available

E.mbrace

A.4.1

Sponsor's protocol code number

VAC52416BAC3001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04899336

A.5.4

Other Identifiers

Name:

IND

Number:

18773

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	Janssen Vaccines & Prevention B.V.
B.1.3.4	Country	Netherlands
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	Janssen Research and Development
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen Research & Development
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 20
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CN
B.5.3.4	Country	Netherlands
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	ExPEC9V
D.3.2	Product code	[JNJ-78901563]
D.3.4	Pharmaceutical form	Solution for injection/infusion
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	EcoO1A
D.3.9.2	Current sponsor code	EcoO1A
D.3.9.3	Other descriptive name	EcoO1A
D.3.9.4	EV Substance Code	SUB221304
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO2
D.3.9.2	Current sponsor code	EcoO2
D.3.9.3	Other descriptive name	EcoO2
D.3.9.4	EV Substance Code	SUB221305
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO4
D.3.9.2	Current sponsor code	EcoO4
D.3.9.3	Other descriptive name	EcoO4
D.3.9.4	EV Substance Code	SUB221306
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO6A
D.3.9.2	Current sponsor code	EcoO6A
D.3.9.3	Other descriptive name	EcoO6A
D.3.9.4	EV Substance Code	SUB221307
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO15
D.3.9.2	Current sponsor code	EcoO15
D.3.9.3	Other descriptive name	EcoO15
D.3.9.4	EV Substance Code	SUB221309
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO16
D.3.9.2	Current sponsor code	EcoO16
D.3.9.3	Other descriptive name	EcoO16
D.3.9.4	EV Substance Code	SUB221310
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO18A
D.3.9.2	Current sponsor code	EcoO18A
D.3.9.3	Other descriptive name	EcoO18A
D.3.9.4	EV Substance Code	SUB221311
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO25B
D.3.9.2	Current sponsor code	EcoO25B
D.3.9.3	Other descriptive name	SUB221312
D.3.9.4	EV Substance Code	EcoO25B
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	32
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EcoO75
D.3.9.2	Current sponsor code	EcoO75
D.3.9.3	Other descriptive name	EcoO75
D.3.9.4	EV Substance Code	SUB221313
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	32
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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Invasive Extraintestinal Pathogenic Escherichia coli Disease

malattia invasiva da escherichia coli patogeno extraintestinale

E.1.1.1

Medical condition in easily understood language

Invasive E. coli disease

malattia invasiva da escherichia coli

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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	10052238
E.1.2	Term	Escherichia urinary tract infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10015295
E.1.2	Term	Escherichia 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 in a hierarchical manner:
- the efficacy of ExPEC9V compared to placebo in the prevention of the first IED event with
microbiological confirmation from blood, other sterile sites, or urine caused by ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75 and
- the efficacy of ExPEC9V compared to placebo in the prevention of the first IED event with microbiological confirmation from blood or other sterile sites caused by ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75

Dimostrare in maniera gerarchica:
¿ L’efficacia del vaccino nonavalente anti-Escherichia coli patogeno extraintestinale (ExPEC9V) rispetto al placebo nella prevenzione del primo evento di malattia invasiva da ExPEC (IED) con conferma microbiologica da sangue, altri siti sterili o urina, causato dai sierotipi O1A, O2, O4, O6A, O15, O16, O18A, O25B e O75 di ExPEC
¿ L’efficacia di ExPEC9V rispetto al placebo nella prevenzione del primo evento IED con conferma microbiologica da sangue o altri siti sterili, causato dai sierotipi O1A, O2, O4, O6A, O15, O16, O18A, O25B e O75 di ExPEC.

E.2.2

Secondary objectives of the trial

To demonstrate the efficacy of ExPEC9V compared to placebo in the prevention of
•all IEDs caused by ExPEC9V O-serotypes
•the first hospitalized IED event caused by ExPEC9V O-serotypes
•the first IED event meeting criteria for sepsis caused by ExPEC9V O-serotypes
•the first bacteremic IED event caused by ExPEC9V O-serotypes
•the first pyelonephritis event caused by ExPEC9V O-serotypes
•the first UTI event caused by ExPEC9V O-serotypes
•all UTIs caused by ExPEC9V O-serotypes
•the first IED event caused by any ExPEC O-serotype
•the first pyelonephritis event caused by any ExPEC O-serotype
•the first UTI event caused by any ExPEC O-serotype
To evaluate:
•the immunogenicity of ExPEC9V in the Immunogenicity Subset
•the safety and reactogenicity of ExPEC9V

Insufficient space, please refer to Protocol

Dimostrare l’efficacia di ExPEC9V rispetto al placebo nella prevenzione di:
• Tutti gli IED causati da O-sierotipi di ExPEC9V
• Primo evento di ricovero per IED causato da O-sierotipi di ExPEC9V
• Primo evento IED che soddisfa i criteri per la sepsi, causato da O-sierotipi di ExPEC9V
• Primo evento IED batteriemico causato da O-sierotipi di ExPEC9V
• Primo evento di pielonefrite causato da O-sierotipi di ExPEC9V
• Primo evento di infezione delle vie urinarie (UTI,) causato da O-sierotipi di ExPEC9V
• Tutte le UTI causate da O-sierotipi di ExPEC9V
• Primo evento IED causato da qualsiasi O-sierotipo di ExPEC
• Primo evento di pielonefrite causato da qualsiasi O-sierotipo di ExPEC
• Primo evento UTI causato da qualsiasi O-sierotipo di ExPEC.
Valutare:
• L’immunogenicità di ExPEC9V nel sottogruppo di immunogenicità
• La sicurezza e la reattogenicità di ExPEC9V

Spazio insufficiente, fare riferimento al Protocollo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Participant must be >=60 years of age on the day of signing the ICF and is expected to be available for the duration of the study, with no current intention of moving away from a study site area or travelling for periods longer than 30 consecutive days during the course of the study.
-Participant must have a history of UTI in the past 2 years that is documented in the medical records. In case of a recent history of UTI, the condition must have resolved >14 days prior to randomization.
-Participant must be medically stable at the time of vaccination such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. A stable medical condition is defined as disease not requiring significant change in therapy during the 6 weeks before enrollment and when hospitalization for worsening of the disease is not anticipated. Participants will be included on the basis of physical examination, medical history, and vital signs performed between ICF signature and vaccination.

-Before randomization, participants who were born female must be either (as defined in Section 10.4, Appendix 4, Contraceptive Guidance and Collection of Pregnancy Information):
a. postmenopausal or permanently sterile, and
b. not intending to conceive by any methods.
-Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
-Participant or his/her designated caregiver must be able to work with smartphones/tablets/computers.
-Participant and his/her designated caregiver (if applicable) must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment (eCOA, ie, the electronic patient-reported outcomes [ePROs] and the eDiary).

¿ Il partecipante deve avere un’età >= 60 anni il giorno della firma del modulo di consenso informato (ICF) e si prevede che sia disponibile per la durata dello studio, senza alcuna intenzione attuale di abbandonare un’area del centro dello studio o viaggiare per periodi superiori a 30 giorni consecutivi nel corso dello studio.
¿ Il partecipante deve avere un’anamnesi di UTI negli ultimi 2 anni documentata nelle cartelle cliniche. In caso di anamnesi recente di UTI, la condizione deve essersi risolta > 14 giorni prima della randomizzazione.
¿ Il partecipante deve essere clinicamente stabile al momento della vaccinazione al punto che, stando al parere dello sperimentatore, non sia previsto il ricovero entro il periodo dello studio e il partecipante sembri probabilmente in grado di rimanere nello studio fino al termine del follow-up specificato dal protocollo. Una condizione medica stabile è definita come una malattia che non richiede un cambiamento significativo nella terapia durante le 6 settimane precedenti l’arruolamento e per cui non si prevede un ricovero in caso di peggioramento della stessa. I partecipanti saranno inclusi sulla base dell’esame obiettivo, dell’anamnesi medica e dei segni vitali eseguiti tra la firma dell’ICF e la vaccinazione.
¿ Prima della randomizzazione, i partecipanti di sesso femminile alla nascita devono essere (come definito nella Sezione 10.4, Appendice 4: Guida alla contraccezione e raccolta di informazioni sulla gravidanza):
a. in post-menopausa o permanentemente sterili e
b. non intenzionati a concepire con qualsiasi metodo.
¿ Il partecipante deve essere disposto a fornire un’identificazione verificabile, deve disporre di mezzi per essere contattato e per contattare lo sperimentatore durante lo studio.
¿ Il partecipante o il suo caregiver designato deve essere in grado di lavorare con smartphone/tablet/computer.
¿ Il partecipante e il suo caregiver designato (se pertinente) devono essere in grado di leggere, comprendere e compilare i questionari nella valutazione elettronica degli esiti clinici (eCOA, ovvero gli esiti riferiti dal paziente in formato elettronico [ePRO] e l’eDiary).

E.4

Principal exclusion criteria

-Participant has a serious chronic disorder or significant cognitive impairment for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- Participant has end-stage renal disease for which dialysis is required.
- Chronic use of antimicrobials. In case of prolonged antimicrobial treatment (>3 weeks) or chronic use of antimicrobials, the last dose must have been administered >60 days prior to randomization.
- Participant has a history of malignancy within 5 years before screening not in the following categories:(a) Participants with curatively treated squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator; (b) Participants with diagnosis of localized prostate cancer may be enrolled at the discretion of the investigator if they completed treatment, or, if they remain under observation or active surveillance; (c) Participants with a history of other malignancy within 5 years, which is considered adequately treated with minimal risk of recurrence per the investigator’s judgment, may be enrolled.
- Participant has a known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine; refer to IB).

- Abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or immunodeficiency).
b. Chronic or recurrent use of systemic corticosteroids
c. Administration of antineoplastic and immunomodulating agents or radiotherapy.

- Participant has a history of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic inflammatory demyelinating polyneuropathy
- Participant has received any E. coli or ExPEC vaccine.
- Participant has received a hematopoietic stem cell transplant based on medical history, treatment with immunoglobulins within 2 months, apheresis therapies within 4 months, or blood products within 4 months prior to the planned administration of the study vaccine or has any plans to receive such treatment during the study.
- Participant has received or plans to receive: (a)licensed live attenuated vaccines - within 28 days before or after planned administration of the study vaccination; (b)other licensed (not live) vaccines - within 14 days before or after planned administration of the study vaccination; (c)vaccination with a licensed or authorized for Emergency Use Authorization, conditional Marketing Authorisation or a similar program) COVID-19 vaccine is permitted when given at least 28 days before or after planned administration of the study vaccination.
- Participant has had major surgery (per the investigator’s judgment) within 4 weeks before dosing or will not have recovered from surgery per the investigator’s judgment at time of vaccination.
- Participant has chronic active hepatitis B or hepatitis C infection based on medical history. Note: participant may have stable HBV or HCV infection.
- Participant has evidence of HIV type 1 or type 2 infection by medical history. Note: participant may have stable/well-controlled HIV.

¿ Il partecipante presenta un disturbo cronico serio o un significativo deficit cognitivo per il quale, stando al parere dello sperimentatore, la partecipazione non sarebbe nel suo migliore interesse (per es., ne comprometterebbe il benessere) o che potrebbe impedire, limitare o confondere le valutazioni specificate dal protocollo.
¿ Il partecipante presenta malattia renale allo stadio terminale per la quale è necessaria la dialisi.
¿ Uso cronico di antimicrobici. In caso di trattamento antimicrobico prolungato (> 3 settimane) o uso cronico di antimicrobici, l’ultima dose deve essere stata somministrata > 60 giorni prima della randomizzazione.
¿ Il partecipante presenta un’anamnesi di tumore maligno nei 5 anni precedenti lo screening e non rientra nelle seguenti categorie: (a) di partecipanti che presentano carcinomi cutanei squamocellulari e basocellulari e carcinoma in situ della cervice trattati radicalmente, che possono essere arruolati a discrezione dello sperimentatore; (b) di partecipanti con diagnosi di carcinoma prostatico localizzato, che possono essere arruolati a discrezione dello sperimentatore se hanno completato il trattamento oppure se rimangono sotto osservazione o sorveglianza attiva; (c) di partecipanti con anamnesi di altra malignità entro 5 anni, considerata adeguatamente trattata dallo sperimentatore con un rischio minimo di recidiva, che possono essere arruolati.

¿ Il partecipante presenta un’allergia o un’anamnesi nota di anafilassi o altre reazioni avverse serie ai vaccini o ai loro eccipienti (compresi, nello specifico, gli eccipienti del vaccino in studio; fare riferimento al Dossier per lo sperimentatore [IB]).

¿ Funzione anomala del sistema immunitario conseguente a:
a. Condizioni cliniche (per es., malattia autoimmune o immunodeficienza).
b. Uso cronico o ricorrente di corticosteroidi sistemici
c. Somministrazione di agenti antineoplastici e immunomodulanti o radioterapia.

¿ Il partecipante presenta un’anamnesi di polineuropatia acuta (per es., sindrome di Guillain-Barré) o polineuropatia demielinizzante infiammatoria cronica.
¿ Il partecipante ha ricevuto qualsiasi vaccino contro E. coli o ExPEC.
¿ Il partecipante ha ricevuto un trapianto di cellule staminali ematopoietiche in base all’anamnesi medica, trattamento con immunoglobuline entro 2 mesi, terapie di aferesi entro 4 mesi o emoderivati entro 4 mesi prima della somministrazione prevista del vaccino in studio o ha in programma di ricevere tale trattamento durante lo studio.
¿ Il partecipante ha ricevuto o prevede di ricevere: (a) vaccini vivi attenuati approvati, nei 28 giorni precedenti o successivi alla somministrazione programmata della vaccinazione dello studio; (b) altri vaccini approvati (non vivi) nei 14 giorni precedenti o successivi alla somministrazione programmata della vaccinazione dello studio; (c) la vaccinazione con un vaccino COVID-19 munito di autorizzazione o approvazione per l’uso in caso di emergenza, di autorizzazione all’immissione in commercio condizionata o programma simile, è ammissibile se somministrata almeno 28 giorni prima o dopo la somministrazione programmata della vaccinazione dello studio.
¿ Il partecipante si è sottoposto a un intervento di chirurgia maggiore (stando al parere dello sperimentatore) nelle 4 settimane precedenti la somministrazione o, secondo lo sperimentatore, al momento della vaccinazione non si sarà ancora ripreso dall’intervento chirurgico.
¿ Il partecipante presenta un’infezione cronica attiva da epatite B o epatite C in base all’anamnesi medica. Nota: il partecipante può presentare infezione stabile da virus dell’epatite B (HBV) o C (HCV).
¿ Il partecipante presenta evidenza di infezione da virus dell’immunodeficienza umana (HIV) di tipo 1 o 2 in base all’anamnesi medica. Nota: il partecipante potrebbe presentare
un’infezione stabile/ben controllata da HIV.

E.5 End points

E.5.1

Primary end point(s)

The primary analysis of the primary endpoints will evaluate:
• the number of participants with at least 1 IED event, with microbiological confirmation in blood, other sterile sites, or urine, caused by ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75 with onset at least 29 days after vaccination (from Day 30) in the active vaccine (ExPEC9V) group compared to the placebo group in the PPE population and
• the number of participants with at least 1 IED event with microbiological confirmation in blood or other sterile sites caused by ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75 with onset at least 29 days after vaccination (from Day 30) in the active vaccine (ExPEC9V) group compared to the placebo group in the PPE population.

L’analisi primaria degli endpoint primari valuterà:
• Il numero di partecipanti con almeno 1 evento IED con conferma microbiologica da sangue, altri siti sterili o urina, causato dai sierotipi O1A, O2, O4, O6A, O15, O16, O18A, O25B e O75 di ExPEC, con insorgenza almeno 29 giorni dopo la vaccinazione (dal Giorno 30) nel braccio assegnato al vaccino attivo (ExPEC9V) rispetto al braccio assegnato al placebo nella popolazione di efficacia per protocollo (PPE) e
• Il numero di partecipanti con almeno 1 evento IED con conferma microbiologica da sangue o altri siti sterili, causato dai sierotipi O1A, O2, O4, O6A, O15, O16, O18A, O25B e O75 di ExPEC con insorgenza almeno 29 giorni dopo la vaccinazione (dal Giorno 30) nel braccio assegnato al vaccino attivo (ExPEC9V) rispetto al braccio assegnato al placebo nella popolazione PPE.

E.5.1.1

Timepoint(s) of evaluation of this end point

• First IED event , with microbiological confirmation from blood, other sterile sites, or urine, caused by ExPEC9V O serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75
•First IED event, with microbiological confirmation from blood or other sterile sites, caused by ExPEC9V O serotypes

• Primo evento IED con conferma microbiologica da sangue, altri siti sterili o urina, causato dagli O-sierotipi O1A, O2, O4, O6A, O15, O16, O18A, O25B e O75 di ExPEC9V
• Primo evento IED con conferma microbiologica da sangue o altri siti sterili, causato da O-sierotipi di ExPEC9V

E.5.2

Secondary end point(s)

•All IEDs (including multiple IEDs per participant) caused by ExPEC9V O serotypes
• First hospitalized IED event caused by ExPEC9V O serotypes
• First IED event meeting criteria for sepsis caused by ExPEC9V O serotypes
• First bacteremic IED event caused by ExPEC9V O serotypes
• First pyelonephritis event caused by ExPEC9V O serotypes
• First UTI event caused by ExPEC9V O serotypes
• All UTIs (including multiple UTIs per participant) caused by ExPEC9V O serotypes
• First IED event caused by any ExPEC O serotype
• First pyelonephritis event caused by any ExPEC O-serotype
• First UTI event caused by any ExPEC O serotype
• Antibody titers to vaccine O-serotype antigens and EPA in the Immunogenicity Subset, as determined by multiplex ECL-based immunoassay and antibody titers to vaccine O-serotype antigens, as determined by multiplex opsonophagocytic killing assay (MOPA) on Day 30, Day 181, Year 1, Year 2, and Year 3
• Solicited local and systemic AEs (collected until 14 days post-vaccination [from Day 1 to Day 15] in the Safety Subset)
• Unsolicited AEs (collected until 29 days post-vaccination [from Day 1 to Day 30] in all participants)
• Serious adverse events (SAEs) in all participants
• SF-36 and EQ-5D-5L responses at scheduled timepoints
• Frailty index as a measure of frailty at baseline, Year 1, Year 2, Year 3, and at the time of an IED
• Medical resource utilization for IED events
• Medical resource utilization for UTI events (Immunogenicity Subset only)
• Hospitalization and length of stay in hospital for IED or UTI events
• IED-related and all-cause mortality
; • Tutte le IED (comprese le IED multiple per partecipante) causate da O-sierotipi di ExPEC9V
• Primo evento di ricovero per IED causato da O-sierotipi di ExPEC9V
• Primo evento IED che soddisfa i criteri per la sepsi, causato da O-sierotipi di ExPEC9V
• Primo evento IED batteriemico causato da O-sierotipi di ExPEC9V
• Primo evento di pielonefrite causato da O-sierotipi di ExPEC9V
• Primo evento UTI causato da O-sierotipi di ExPEC9V
• Tutte le UTI (comprese UTI multiple per partecipante) causate da O-sierotipi di ExPEC9V
• Primo evento IED causato da qualsiasi O-sierotipo di ExPEC
• Primo evento di pielonefrite causato da qualsiasi O-sierotipo di ExPEC
• Primo evento UTI causato da qualsiasi O-sierotipo di ExPEC
• Titoli anticorpali contro gli antigeni vaccinali del sierotipo O ed Esotossina A derivante da Pseudomonas aeruginosa (EPA) nel sottogruppo di immunogenicità, come determinato mediante immunodosaggio basato su elettrochemiluminescenza (ECL) con metodo multiplex e titoli anticorpali contro gli antigeni vaccinali del sierotipo O, come determinato mediante test di uccisione opsonofagocitica multiplex (MOPA) al Giorno 30, Giorno 181, Anno 1, Anno 2 e Anno 3
• Eventi avversi (EA) locali e sistemici richiesti (raccolti fino a 14 giorni dopo la vaccinazione [dal Giorno 1 al Giorno 15] nel sottogruppo di sicurezza)
• EA non richiesti (raccolti fino a 29 giorni dopo la vaccinazione [dal Giorno 1 al Giorno 30] in tutti i partecipanti)
• Eventi avversi gravi (SAE) in tutti i partecipanti
• Risposte fornite al modulo breve a 36 voci (SF-36) e al questionario a 5 dimensioni con scala a 5 livelli (EQ-5D-5L), per misurare la qualità della vita, in corrispondenza di momenti definiti programmati
• Indice di fragilità come misura della fragilità al basale, all’Anno 1, Anno 2, Anno 3 e al verificarsi di una IED
• Utilizzo delle risorse mediche per eventi IED
• Utilizzo delle risorse mediche per eventi UTI (solo sottogruppo di immunogenicità)
• Ricovero e durata della degenza ospedaliera per eventi IED o UTI
• Mortalità correlata alla IED e per qualsiasi causa

E.5.2.1

Timepoint(s) of evaluation of this end point

As described in section E.5.2

Come descritto nella sezione E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

Canada

Israel

Japan

Korea, Republic of

New Zealand

Taiwan

United States

France

Sweden

Netherlands

Spain

Czechia

Germany

Italy

Denmark

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

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

The end of study is considered as the last Year 3 assessment (Day 1096) for the last participant in Part 2.

La fine dello studio è considerata l'ultima valutazione dell'anno 3 (giorno 1096) per l'ultimo partecipante nella parte 2.

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:

3712

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

14844

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3700

F.4.2.2

In the whole clinical trial

18556

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

2022-09-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-09-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials