Clinical Trials Register

Summary
EudraCT Number:	2020-004061-39
Sponsor's Protocol Code Number:	CNTO1959PSO4015
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:	2021-10-12
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004061-39

A.3

Full title of the trial

A Phase 4, Interventional, Single-arm, Open-label Study Evaluating the Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis

Studio di fase 4, interventistico, a braccio singolo, in aperto volto a valutare l’effetto di guselkumab sui marcatori surrogati del rischio cardiovascolare nei partecipanti con psoriasi a placche da moderata a grave

A.3.1

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

Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Patients With Moderate to Severe Plaque Psoriasis

Effetto di guselkumab sui marcatori surrogati del rischio cardiovascolare nei partecipanti con psoriasi a placche da moderata a grave

A.3.2

Name or abbreviated title of the trial where available

G-CARE

----

A.4.1

Sponsor's protocol code number

CNTO1959PSO4015

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 CILAG INTERNATIONAL NV
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	Janssen Pharmaceutica NV
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	PAREXEL International IRL
B.5.2	Functional name of contact point	------
B.5.3	Address:
B.5.3.1	Street Address	----------------
B.5.3.2	Town/ city	----------------
B.5.3.3	Post code	---------------
B.5.3.4	Country	Ireland
B.5.4	Telephone number	0000000000
B.5.5	Fax number	00000000
B.5.6	E-mail	clinicaltrial.enquiries@parexel.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	Yes
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	adenosina
D.3.2	Product code	[-------]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	adenosina
D.3.9.2	Current sponsor code	-----
D.3.10	Strength
D.3.10.1	Concentration unit	µg/kg microgram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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.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	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	Guselkumab
D.3.2	Product code	[CNTO1959]
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CNTO1959
D.3.9.3	Other descriptive name	GUSELKUMAB
D.3.9.4	EV Substance Code	SUB179789
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo Monoclonale

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

Plaque Psoriasis

Psoriasi a placche

E.1.1.1

Medical condition in easily understood language

Psoriasis

Psoriasi

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

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	10071117
E.1.2	Term	Plaque psoriasis
E.1.2	System Organ Class	100000004858

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	10071117
E.1.2	Term	Plaque psoriasis
E.1.2	System Organ Class	100000004858

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 effect of guselkumab on CFR measured by transthoracic dopplerechocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk

Valutare l’effetto di guselkumab sulla riserva di flusso coronarico (CFR) misurata con ecocardiografia doppler transtoracica nei partecipanti con psoriasi da moderata a grave e rischio cardiovascolare intermedio

E.2.2

Secondary objectives of the trial

- To evaluate the short-term effect of guselkumab on CFR measured by transthoracic dopplere-chocardiography, in participants with moderateto- severe psoriasis and intermediate cardiovascular risk.
-To evaluate the effect of guselkumab on GLS as a surrogate marker of left ventricular function in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
- To evaluate the effect of guselkumab on arterial stiffness in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
- To evaluate the effect of guselkumab on CFR among participants in the different CFR categories.
- To evaluate the effect of guselkumab on surrogate CV risk markers among nicotine users and non-users in the participant population.
- To assess the safety and tolerability of guselkumab in participants with moderate-to severe plaque psoriasis and intermediate cardiovascular risk

- Valutare l’effetto a breve termine di guselkumab sulla CFR misurata con ecocardiografia doppler transtoracica nei partecipanti con psoriasi da moderata a grave e rischio cardiovascolare intermedio.
- Valutare l’effetto di guselkumab sullo strain globale longitudinale (GLS) come marcatore surrogato della funzione ventricolare sinistra nei partecipanti con psoriasi da moderata a grave e rischio cardiovascolare
-Valutare l’effetto di guselkumab sulla rigidità arteriosa nei partecipanti con psoriasi da moderata a grave e rischio cardiovascolare intermedio.
-Valutare l’effetto di guselkumab sulla CFR tra i partecipanti nelle diverse categorie di CFR.
- Valutare l’effetto di guselkumab sui marcatori surrogati di rischio CV tra consumatori e non consumatori di nicotina nella popolazione dei partecipanti
- Valutare la sicurezza e la tollerabilità di guselkumab nei partecipanti con psoriasi a placche da moderata a grave e rischio cardiovascolare intermedio..

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Is male or female 18 years of age and above.
- Has a diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to the first dose of guselkumab at Week 0. Moderate-tosevere plaque psoriasis is defined as PASI >=12, IGA >=3 and involved BSA
>=10% at Screening Visit S1. Participants with a predominantly non plaque form of psoriasis will not be eligible for inclusion in the study.
-Has intermediate cardiovascular risk defined by CFR >=2 to <=3.5.
- Is a candidate for systemic treatment for psoriasis.
- Does not have any abnormalities in physical examination, medical history, clinical laboratory tests, vital signs, and 12-lead ECG performed at screening that are not consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed by the investigator. The 12-lead ECG
must be assessed by the dermatologist at Screening Visit S1.
- Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
For the complete overview of the inclusion criteria, please refer to section 5.1 of the protocol.

- È maschio o femmina di età pari o superiore a 18 anni.
- Ha una diagnosi di psoriasi a placche da moderata a grave per almeno 6 mesi prima della prima dose di guselkumab alla settimana 0. La psoriasi a placche da moderata a grave è definita come PASI > =12, IGA > =3 e BSA coinvolta > =10% alla visita di screening S1. I partecipanti con una forma prevalentemente non a placche di psoriasi non saranno eleggibili per l'inclusione nello studio.
-Ha un rischio cardiovascolare intermedio definito da CFR da > =2 a <=3,5.
- È un candidato per il trattamento sistemico della psoriasi.
- Non presenta anomalie nell'esame obiettivo, nell'anamnesi, nei test clinici di laboratorio, nei segni vitali e nell'ECG a 12 derivazioni eseguito allo screening che non sono coerenti con la malattia sottostante nella popolazione in studio. Questa determinazione deve essere registrata nei documenti clinici del partecipante e siglata dallo sperimentatore. L'ECG a 12 derivazioni deve essere valutato dal dermatologo alla visita di screening S1.
- Deve firmare un modulo di consenso informato (ICF) indicando che comprende lo scopo e le procedure richieste per lo studio ed è disposto a partecipare allo studio.
Per la panoramica completa dei criteri di inclusione, fare riferimento alla sezione 5.1 del protocollo.

E.4

Principal exclusion criteria

- Has low-density lipoprotein >160 mg/dL.
- Has uncontrolled hypertension that needs immediate medication
- Has any clinically significant evidence of cardiac functional or valvular abnormalities, other than intermediate cardiovascular risk defined by CFR > = 2 and <=3.5, including but not limited to: coronary stenosis, history of any MI or transient ischemic attacks, stroke, cerebrovascular disease, peripheral atherosclerosis, congestive heart failure, chronic pulmonary disease, fast atrial fibrillation, supraventricular arrhythmia, valvular
abnormalities, ventricular wall movement abnormalities observed during the CFR assessment
- Has any contraindications to adenosine infusion, including but not limited to asthma with ongoing wheezing, hypersensitivity to adenosine, known or suspected bronchoconstrictive or bronchospastic lung disease, greater than first degree heart block without a pacemaker or sick sinus syndrome, systolic blood pressure <90 mmHg and severe sinus
bradycardia, or other contraindications listed in the SmPC.
- Unable or unwilling to abstain from caffeine-or nicotine-containing products including but not limited to smoking, vaping, chewing tobacco, nicotine gum and patches for 12
hours prior to the cardiology assessments.
- Has diabetes or has HbA1c >6.5.
For the complete overview of the inclusion criteria, please refer to
section 5.2 of the protocol.

- Ha lipoproteine a bassa densità> 160 mg / dL.
- Ha ipertensione incontrollata che necessita di cure immediate
- Ha qualsiasi evidenza clinicamente significativa di funzionalità cardiaca o valvolare anomalie, diverse dal rischio cardiovascolare intermedio definito da CFR > =2 e <=3,5, inclusi ma non limitati a: stenosi coronarica, anamnesi di qualsiasi IM o attacchi ischemici transitori, ictus, malattie cerebrovascolari, aterosclerosi periferica, insufficienza cardiaca congestizia, polmonare cronica malattia, fibrillazione atriale rapida, aritmia sopraventricolare, valvolare anomalie, anomalie del movimento della parete ventricolare osservate durante la valutazione CFR
- Ha controindicazioni all'infusione di adenosina, incluso ma non limitato all'asma con respiro sibilante in corso, ipersensibilità all'adenosina, malattia polmonare broncocostrittiva o broncospastica nota o sospetta, blocco cardiaco maggiore del primo grado senza pacemaker o seno malato sindrome, pressione sanguigna sistolica <90 mmHg e seno grave bradicardia o altre controindicazioni elencate nell'RCP.
- Incapace o riluttante ad astenersi dal consumo di caffeina o nicotina prodotti inclusi ma non limitati a fumo, svapo, tabacco da masticare, gomme alla nicotina e cerotti per 12 ore prima delle valutazioni cardiologiche. –
Ha il diabete o ha HbA1c> 6.5.
Per la panoramica completa dei criteri di inclusione, fare riferimento a sezione 5.2 del protocollo

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in CFR

Variazione rispetto al basale nella CFR

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 32

Settimana 32

E.5.2

Secondary end point(s)

- Change from baseline in CFR at Week 16
- Change from baseline in GLS at Week 32 and change from baseline in GLS at Week 16
- Change from baseline in cfPWV at Week 32 and change from baseline in cfPWV at Week 16.
- Change from baseline in CFR at Week 16 and Week 32 among participants with CFR in the ranges of 2 to 2.49, 2.5 to 3, and 3.01 to 3.5 at baseline
- Change from baseline in CFR at Week 16 and Week 32 among nicotine users and non-users.
- Change from baseline in GLS at Week 16 and Week 32 among nicotine users and non-users.
- Change from baseline in cfPWV at Week 16 and Week 32 in nicotine users and non-users
- Rate of AEs among participants treated with guselkumab.

- Variazione rispetto al basale nella CFR alla Settimana 16
- Variazione rispetto al basale nel GLS alla Settimana 32e variazione rispetto al basale nel GLS alla Settimana 16
- Variazione rispetto al basale nella velocità dell’onda di polso carotideo-femorale (cfPWV) alla Settimana 32 e variazione rispetto al basale nel cfPWV alla settimana 16
- Variazione rispetto al basale nella CFR alla Settimana 16 e alla Settimana 32 tra i partecipanti con CFR negli intervalli da 2 a 2,49, da 2,5 a 3 e da 3,01 a 3,5 al basale.
- Variazione rispetto al basale nella CFR alla Settimana 16 e alla Settimana 32 tra consumatori e non consumatori di nicotina.
- Variazione rispetto al basale nel GLS alla Settimana 16 e alla Settimana 32 tra consumatori e non consumatori di nicotina.
- Variazione rispetto al basale nella cfPWV alla Settimana 16 e alla Settimana 32 tra consumatori e non consumatori di nicotina.
- Tasso di EA tra i partecipanti trattati con guselkumab.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16 and 32

Settimana 16 e 32

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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

Biomarker

Biomarcatori

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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 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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

2021-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-24

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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