Clinical Trials Register

Summary
EudraCT Number:	2018-003988-54
Sponsor's Protocol Code Number:	GDX-44-010
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:	2021-01-21
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

2018-003988-54

A.3

Full title of the trial

Efficacy and Safety of gadoPIClenol for CenTral NervoUs System (CNS) Magnetic REsonance Imaging (MRI)

Efficacia e sicurezza di gadopiclenol per la risonanza magnetica (RM) del sistema nervoso centrale (SNC)

A.3.1

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

Evaluation of Gadopiclenol for central nervous system magnetic resonance imaging

Valutazione di gadopiclenol per la risonanza magnetica del sistema nervoso centrale

A.3.2

Name or abbreviated title of the trial where available

The PICTURE trial

sperimentazione PICTURE

A.4.1

Sponsor's protocol code number

GDX-44-010

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	GUERBET
B.1.3.4	Country	France
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	Guerbet
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Guerbet
B.5.2	Functional name of contact point	Lucie Begert
B.5.3	Address:
B.5.3.1	Street Address	B.P. 57400
B.5.3.2	Town/ city	Roissy CdG Cedex
B.5.3.3	Post code	95943
B.5.3.4	Country	France
B.5.4	Telephone number	0033145917201
B.5.5	Fax number	0033145915199
B.5.6	E-mail	lucie.begert@guerbet.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	gadopiclenol
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Solution for injection
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	gadopiclenol
D.3.9.1	CAS number	933983-75-6
D.3.9.2	Current sponsor code	P03277, G03277
D.3.9.4	EV Substance Code	SUB194566
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/l millimole(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	Comparator
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	Gadovist 1.0 mmol/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	gadobutrolo
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Solution for injection
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	gadobutrolo
D.3.9.1	CAS number	138071-82-6
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	gadobutrol
D.3.9.4	EV Substance Code	SUB07861MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mol/l mole(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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.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

Patient presenting with known or highly suspected CNS lesion(s) with focal areas of disrupted Blood Brain Barrier (e.g., primary and secondary tumors)

Pazienti che presentano una o più lesioni del SNC note o altamente sospette con aree focali di barriera emato-encefalica interrotta (ad es. tumori primari e secondari)

E.1.1.1

Medical condition in easily understood language

Brain lesion

Lesioni cerebrali

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.1
E.1.2	Level	LLT
E.1.2	Classification code	10056922
E.1.2	Term	MRI brain abnormal
E.1.2	System Organ Class	100000004848

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.1
E.1.2	Level	LLT
E.1.2	Classification code	10056941
E.1.2	Term	MRI brain
E.1.2	System Organ Class	100000004848

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 superiority of gadopiclenol-enhanced MRI at 0.05 mmol/kg body weight (BW) compared to unenhanced MRI for patient referred for contrast-enhanced MRI of CNS, in terms of 3 lesion visualization co-primary criteria using the patient as his/her own control.
- To demonstrate the non-inferiority of gadopiclenol at 0.05 mmol/kg compared to gadobutrol at 0.1 mmol/kg in terms of 3 lesion visualization co-primary criteria for patient referred for contrast-enhanced MRI of CNS.

- Dimostrare la superiorità della RM con contrasto di gadopiclenol a 0,05 mmol/kg di peso corporeo (PC) rispetto alla RM senza contrasto per pazienti che devono sottoporsi a RM con contrasto del SNC, in termini di 3 criteri co-primari di visualizzazione delle lesioni utilizzando il paziente come proprio controllo.
- Dimostrare la non inferiorità di gadopiclenol a 0,05 mmol/kg rispetto al gadobutrolo a 0,1 mmol/kg in termini di 3 criteri co-primari di visualizzazione delle lesioni per paziente che devono sottoporsi a RM con contrasto del SNC.

E.2.2

Secondary objectives of the trial

- To assess visualization parameters with gadopiclenol and gadobutrol
- To assess the safety profile of gadopiclenol and gadobutrol

- Valutare la visualizzazione dei parametri con gadopiclenol e gadobutrolo
- Valutare il profilo di sicurezza di gadopiclenol e gadobutrolo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Female or male adult patient (patient having reached legal majority age).
- Patient presenting with known or highly suspected CNS lesion(s) with focal areas of disrupted Blood Brain Barrier (e.g., primary and secondary tumors) based on results of a previous imaging procedure such as Computed Tomography (CT) or MRI, which should have been performed within 12 months prior to ICF signature.
- Patient scheduled for a CNS contrast-enhanced MRI examination for clinical reasons and agreeing to have a second contrast-enhanced MRI examination for the purpose of the trial.
- Patient having read the information and having provided his/her consent to participate in writing by dating and signing the informed consent prior to any trial related procedure being conducted.
Some other inclusion criteria are listed in the trial protocol

- Pazienti adulti (che abbiano raggiunto la maggiore età) di sesso maschile o femminile.
- Pazienti che si presentano con una o più lesioni del SNC note o altamente sospette e caratterizzate da aree focali di barriera emato-encefalica interrotta (per es. tumori primari e secondari) in base ai risultati di una precedente procedura di diagnostica per immagini, come tomografia computerizzata (TC) o RM, che deve essere stata eseguita entro 12 mesi prima della firma dell’ICF.
- Pazienti che hanno in programma di sottoporsi a un esame di RM del SNC con mezzo di contrasto per ragioni cliniche e che acconsentono a sottoporsi a un secondo esame di RM con mezzo di contrasto per lo scopo della sperimentazione.
- Il paziente deve aver letto l’informativa e fornito il proprio consenso a partecipare per iscritto datando e firmando il consenso informato prima che venga effettuata qualsiasi procedura correlata alla sperimentazione.

Gli altri criteri di inclusione sono inclusi nel protocollo.

E.4

Principal exclusion criteria

- Patient presenting extra cranial lesions and/or extra-dural lesions.
- Patient presenting with an acute relapse of multiple sclerosis as qualifying CNS lesion.
- Patient presenting with any contraindication to MRI examinations.
- Patient previously randomized in this trial.
- Patient having received any contrast agent (MRI or CT) within 3 days prior to first trial product administration, or scheduled to receive any contrast agent during the course of the trial or within 24 hours after the second trial product administration.
Some other exclusion criteria are listed in the trial protocol

- Pazienti che presentano lesioni extracraniche e/o lesioni extradurali.
- Pazienti che presentano una recidiva acuta di sclerosi multipla come lesione del SNC qualificante.
- Pazienti che presentano una qualsiasi controindicazione agli esami di RM
- Pazienti precedentemente randomizzati in questa sperimentazione.
- Pazienti che hanno ricevuto qualsiasi agente di contrasto (RM o TC) nei 3 giorni precedenti alla prima somministrazione del prodotto sperimentale o che hanno in programma di ricevere qualsiasi agente di contrasto durante il corso della sperimentazione o entro 24 ore dopo la seconda somministrazione del prodotto sperimentale.

Gli altri criteri di esclusione sono inclusi nel protocollo.

E.5 End points

E.5.1

Primary end point(s)

Lesion visualization criteria based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with
gadopiclenol (criteria 1) and the MRI performed with gadopiclenol and those performed with gadobutrol (criteria 2)

Visualizzazione della lesione basata su 3 criteri co-primari: delineazione dei margini, morfologia interna e grado di miglioramento del contrasto, valutata sulle immagini acquisite durante RM effettuate con gadopiclenol (criterio 1) e RM effettuate con gadopiclenol e quelle effettuate con gadobutrolo (criterio 2).

E.5.1.1

Timepoint(s) of evaluation of this end point

After the 2nd contrast injection / MRI

Dopo la seconda iniezione con contrasto / RM.

E.5.2

Secondary end point(s)

Visualization parameters with gadopiclenol and gadobutrol (e.g. lesion visualization assessment by investigator, number, size and location of lesions ...)
Safety profile of gadopiclenol and gadobutrol

Parametri di visualizzazione con gadopiclenol e gadobutrolo (ad es. visualizzazione della lesione secondo lo Sperimentatore, numero, dimensione e sede delle lesioni...)
Profilo di sicurezza di gadopiclenol e gadobutrolo.

E.5.2.1

Timepoint(s) of evaluation of this end point

After the 2nd contrast injection / MRI
At the end of the patient's participation

Dopo la seconda iniezione con contrasto / RM.
Alla fine della partecipazione del paziene

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

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

E.8.1.6

Cross over

Yes

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

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

Korea, Republic of

Mexico

Taiwan

United States

Belgium

Bulgaria

France

Germany

Hungary

Italy

Poland

Spain

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

The trial will be considered as completed once all the images collected for all the patients will have been reviewed by all the independent blinded readers.

Lo studio sarà considerato completato quando tutte le immagini raccolte per tutti i pazienti saranno state riviste da tutti i lettori indipendenti in cieco.

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:

200

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

135

F.4.2.2

In the whole clinical trial

247

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

2019-06-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-04

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

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