Clinical Trials Register

Summary
EudraCT Number:	2011-006135-29
Sponsor's Protocol Code Number:	PH-107
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:	2012-09-03
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-006135-29

A.3

Full title of the trial

PHASE IV, DOUBLE-BLIND, MULTI-CENTER, RANDOMIZED, CROSSOVER STUDY TO COMPARE 0.1 mmol/kg OF PROHANCE WITH 0.1 mmol/kg OF GADOVIST/GADAVIST IN MAGNETIC RESONANCE IMAGING (MRI) OF THE BRAIN (TRUTH)

STUDIO CLINICO DI FASE IV, IN DOPPIO CIECO, MULTICENTRICO, RANDOMIZZATO, IN CROSS-OVER PER IL CONFRONTO DI UNA DOSE DA 0,1 mmol/kg DI PROHANCE CON 0,1 mmol/kg DI GADOVIST/GADAVIST NELLA RISONANZA MAGNETICA DEL CERVELLO (TRUTH)

A.3.1

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

Comparison between ProHance and Gadovist at the same dose in magnetic resonance of the brain

Confronto tra ProHance e Gadovist/Gadavist somministrati alla stessa dose nella risonanza magnetica del cervello

A.3.2

Name or abbreviated title of the trial where available

TRUTH

A.4.1

Sponsor's protocol code number

PH-107

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	BRACCO IMAGING
B.1.3.4	Country	Italy
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	Bracco Imaging S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bracco Imaging
B.5.2	Functional name of contact point	Global Medical & Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Via XXV Aprile, 4
B.5.3.2	Town/ city	San Donato Milanese
B.5.3.3	Post code	20097
B.5.3.4	Country	Italy
B.5.4	Telephone number	0221772860
B.5.5	Fax number	0221772784
B.5.6	E-mail	valeria.detullio@bracco.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.2.1.1.1	Trade name	PROHANCE*EV FL 20ML 279,3MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	BRACCO IMAGING ITALIA Srl
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.3.4	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	GADOTERIDOL
D.3.9.1	CAS number	120066-54-8
D.3.9.4	EV Substance Code	SUB07866MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/kg millimole(s)/kilogram
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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*FL 15ML 1,0MMOL/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER SpA
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.3.4	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	GADOBUTROL
D.3.9.1	CAS number	138071-82-6
D.3.9.4	EV Substance Code	SUB07861MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mol/kg mole(s)/kilogram
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

Have confirmed or are highly suspected of brain disease likely to enhance as determined by the following: clinical/neurological symptomatology; diagnostic testing, such as CT or previous MRI examinations; or have had previous brain surgery and are to be evaluated for recurrence.

Pazienti con diagnosi o sospettati di avere malattie cerebrali, con sintomatologia clinica e/o neurologica, o già sottoposti a indagini strumentali come TAC o Risonanza Magnetica, o che sono stati già sottoposti a interventi cerebrali e che devono essere ricontrollati.

E.1.1.1

Medical condition in easily understood language

Patients with lesion of the brain of various origin.

Pazienti con lesioni cerebrali di varia natura.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10029820
E.1.2	Term	Nuclear magnetic resonance imaging gadolinium-enhanced
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective for this study is to show non-inferiority of a 0.1 mmol/kg dose of PROHANCE as compared to 0.1 mmol/kg dose of GADOVIST, in terms of the by-subject global diagnostic preference between exams.

L'obiettivo principale di questo studio è dimostrare la non inferiorità di una dose di ProHance di 0.1 mmol/kg rispetto a una dose di 0.1 mmol/kg di Gadovist in termini di preferenza diagnostica globale tra gli esami.

E.2.2

Secondary objectives of the trial

a)To compare the two different investigational products, 0.1 mmol/kg PROHANCE and 0.1 mmol/kg GADOVIST, in terms of by-subject global diagnostic preference between exams in the following secondary endpoints: • Border delineation of lesions • Contrast enhancement of lesions • Lesion Internal Morphology • Extent of Disease b)To compare the two different investigational products in terms of changes from predose to postdose for the following quantitative parameters (signal intensity characteristics): • Lesion-to-background (brain) ratio (LBR) by lesion • Contrast-to-noise ratio (CNR) by lesion • Lesion signal intensity enhancement c)To compare the two different investigational products using the final clinical on-site diagnosis from all available clinical and imaging data as the reference standard in terms of the accuracy of the MR diagnosis of brain disease

a)comparare i due diversi prodotti sperimentali, 0.1 mmol/kg PROHANCE e 0.1 mmol/kg GADOVIST, in terminidi preferenza globale diagnistica intra soggetto nei seguenti endpoint secondari: • delineazione dei bordi delle lesioni; • aumento del contrasto delle lesioni; • morfologia interna della lesione; • estensione della malattia. b) comparare i due prodotti sperimentali in termini di cambio dal predose al post dose per i seguenti parametri quantitativi (caratteristiche dell'intensità del segnale): • rapporto lesione/sfondo(cervello) nella lesione; • rapporto contrasto/rumore di fondo (CNR) nella lesione; • aumento dell'intensità del segnale della lesione. c)paragonare i due prodotti sperimentali usando la diagnosi clinica finale presso il centro da tutti i dati di imaging e clinici come riferimento standard in termini di accuratezza della diagnosi tramite risonanaza della malattia cerebra

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Enroll subjects in this study if they meet the following inclusion criteria: • Are at least 18 years of age or older • Are able to give written informed consent and are willing to comply with the protocol requirements • Are scheduled to undergo MRI • Are willing to undergo two MRI procedures within 14 days • Have confirmed or are highly suspected of brain disease likely to enhance as determined by the following: • clinical/neurological symptomatology; • diagnostic testing, such as CT or previous MRI examinations; or • have had previous brain surgery and are to be evaluated for recurrence.

• Età minima di 18 anni; • In grado di fornire un consenso informato scritto e di soddisfare le richieste del protocollo; • Soggetti per i quali è programmata una risonanza magnetica; • Sono disposti a sottoporsi a due risonanze nel giro di 14 giorni; • Presentano una malattia cerebrale, sospetta o conclamata, che probabilmente aumenterà come determinato dai seguenti parametri: • Sintomatologia clinica/neurologica; • Test diagnostici, come una tac o una risonanza; • Sono stati precedentemente sottoposti a chirurgia cerebrale e devono essere ricontrollati per la ricomparsa.

E.4

Principal exclusion criteria

Exclude subjects from this study if they do not fulfill the inclusion criteria, or if any of the following conditions are observed. • Are pregnant or lactating females. Exclude the possibility of pregnancy: • by testing on site at the institution (serum or urine HCG) within 24 hours prior to the start of each investigational product administration; or • by history (i.e., tubal ligation or hysterectomy); or • post menopausal with a minimum of 1 year without menses • Have any known allergy to one or more of the ingredients in the investigational products, or have a history of hypersensitivity to any metals • Have congestive heart failure (class IV according to the classification of the New York Heart Association; see Appendix A) • Have suffered a stroke within a year • Have received or are scheduled to receive any other contrast medium in the 24 hours preceding through the 24 hours following Exam 1, and in the 24 hours preceding through the 24 hours following Exam 2 • Have received or are scheduled to receive an investigational compound and/or medical device within 30 days before admission into the present study, through the 24 hours post-administration of the second investigational product. • Have moderate-to-severe renal impairment, defined as a GFR/eGFR < 45 mL/min. • Have been previously entered into this study • Have received or are scheduled for one of the following: • Surgery within three weeks prior to the first examination or between the two examinations • Initiation of steroid therapy between the two examinations • Radiosurgery between the two examinations • Have any contraindications to MRI such as a pace-maker, magnetic material (i.e., surgical clips) or any other conditions that would preclude proximity to a strong magnetic field. • Are suffering from severe claustrophobia • Have any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations

• Donne in gravidanza o allattamento. Deve essere esclusa la possibilità di una gravidanza: • Con un test presso il centro (HCG nel sangue o nelle urine) nelle 24 ore precedenti la somministrazione di ciascun prodotto sperimentale; o • Tramite la storia medica (per es., isterectomia o sterilizzazione tubarica); o • Periodo post menopausa con un minimo di un anno senza mestruazioni • Soffrono di un’allergia conosciuta a uno o più ingredienti contenuti nei prodotti sperimentali o hanno una storia di ipersensibilità a un qualunque metallo; • Soffrono di insufficienza cardiaca congestizia (classe IV secondo la classificazione della New York Heart Association); • Hanno sofferto di colpo apoplettico nell’ultimo anno; • E’ stato somministrato o è prevista la somministrazione di qualunque altro mezzo di contrasto dalle 24 ore precedenti alle 24 ore successive all’esame 1 e dalle 24 ore precedenti alle 24 ore successive all’esame 2; • E’ stato somministrato o è prevista la somministrazione di un prodotto sperimentale e/o un dispositivo medico entro i 30 giorni precedenti l’arruolamento fino a 24 ore dopo la somministrazione del secondo prodotto sperimentale; • Soffrono di insufficienza renale da moderata a grave (definita come GFR/eGFR < 45 mL/min); • Sono stati precedentemente arruolati in questo studio; • Pazienti che sono stati sottoposti o per i quali è programmata una delle seguenti: • Intervento chirurgico entro 3 settimane prima del primo esame o tra i due esami • Inizio di terapia steroidea tra i due esami • Radiochirurgia tra i due esami • Presentano una qualunque controindicazione alla risonanza come presenza di pace-maker, materiali magnetici (per es., clip chirurgiche) o qualunque altra condizione che impedisce la vicinanza a forti campi magnetici • Soffrono di claustrofobia grave • Soffrono di qualuque altra condizione medica o alter circostanze che diminuirebbero significativamente la possibilità di ottenere dati affidabili, raggiungere gli obiettivi dello studio e/o gli esami di follow-up post dose.

E.5 End points

E.5.1

Primary end point(s)

Non-inferiority of ProHance compared to Gadovist in the diagnosis of MR examination in brain diseases.

Non inferiorità di ProHance rispetto a Gadovist nella diagnosi delle malattie cerebrali attraverso esame di risonanza.

E.5.1.1

Timepoint(s) of evaluation of this end point

2 days

2 giorni

E.5.2

Secondary end point(s)

• Border delineation of lesions • Contrast enhancement of lesions • Lesion Internal Morphology • Extent of Disease • Lesion-to-background (brain) ratio (LBR) by lesion • Contrast-to-noise ratio (CNR) by lesion • Lesion signal intensity enhancement

• delineazione dei bordi delle lesioni; • aumento del contrasto delle lesioni; • morfologia interna della lesione; • estensione della malattia.• rapporto lesione/sfondo(cervello) nella lesione; • rapporto contrasto/rumore di fondo (CNR) nella lesione; • aumento dell'intensità del segnale della lesione.

E.5.2.1

Timepoint(s) of evaluation of this end point

2 days

2 giorni

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

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

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Conclusion of off-site assessment of all images of the study.

Fine della valutazione centralizzata di tutte le immagini derivanti dallo studio.

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

Number of subjects for this age range:

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:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-09-03.

Yes

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

Yes

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

150

F.4.2.2

In the whole clinical trial

206

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 plans for treatment or care after has ended his/her participation in the trial.

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

2012-10-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-03

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