Clinical Trials Register

Summary
EudraCT Number:	2011-005909-79
Sponsor's Protocol Code Number:	PRIGA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-28
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

Spain - AEMPS

A.2

EudraCT number

2011-005909-79

A.3

Full title of the trial

Magnetic resonance with gadoxetic acid for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. Evaluation of its impact for the non-invasive diagnosis.

Resonancia magnética con Ácido Gadoxético disodio en el diagnóstico del carcinoma hepatocelular en pacientes con cirrosis hepática. Impacto en el diagnóstico no invasivo de la lesión.

A.3.1

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

Gadoxetic acid for the diagnosis of hepatocellular carcinoma in cirrhotic patients

A.4.1

Sponsor's protocol code number

PRIGA

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	Fundació Clínic per a la Recerca Biomèdica
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer Hispania S.L.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinical Trials Unit (CTU)
B.5.2	Functional name of contact point	CTU Clinic (UASP)
B.5.3	Address:
B.5.3.1	Street Address	Villarroel 170
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	00349322754003343
B.5.5	Fax number	0034932279877
B.5.6	E-mail	svarea@clinic.ub.es

D. IMP Identification
D.IMP: 1
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
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Hispania S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Gadovist
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.3.9.1	CAS number	138071-82-6
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	mmol/ml millimole(s)/millilitre
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	Yes
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	Yes
D.2.1.1.1	Trade name	Primovist
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Hispania S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Primovist
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	GADOXETIC ACID
D.3.9.1	CAS number	135326-11-3
D.3.9.4	EV Substance Code	SUB07868MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/ml millimole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
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	Yes
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

hepatocellular carcinoma

Carcinoma Hepatocelular

E.1.1.1

Medical condition in easily understood language

hepatocellular carcinoma

carcinoma hepatocelular

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10049010
E.1.2	Term	Carcinoma hepatocellular
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 establish the diagnostic accuracy of magnetic resonance imaging with gadoxetate disodium for the diagnosis of hepatocellular carcinoma that do not fulfil the established diagnostic criteria as per current guidelines of AASLD (American Association for the Study of Liver Diseases)

Establecer la precisión diagnóstica de la resonancia magnética realzada con gadoxetato de disodio en fases dinámicas y hepatobiliar en el diagnóstico del carcinoma hepatocelular que no cumple los criterios de diagnóstico no invasivo propuestos por las guías actuales de la AASLD (American Association for the Study of Liver Diseases).

E.2.2

Secondary objectives of the trial

1-To define the imaging patterns of hepatocellular carcinoma in cirrhotic patients when studied with gadoxetic acid magnetic resonance imaging including the dynamin phase and the hepatobiliary phase at 10 and 20 minutes after contrast injection
2- To evaluate the usefulness of liver magnetic resonance imaging with gadoxetic acid in the differenciation between bening and malignant nodules in the cirrhotic liver.
3- To determine the diagnosis and clinical significance of the infracentimetric additional nodules detected in the hepatobiliary phase

1- Definir el patrón de imagen del carcinoma hepatocelular en pacientes cirróticos estudiados mediante resonancia magnética con gadoxetato de disodio incluyendo las fases dinámica y hepatobiliar a los 10 y 20 minutos tras la inyección del contraste.
2- Evaluar la utilidad de la resonancia magnética hepática con gadoxetato de disodio para la diferenciación entre nódulos benignos y malignos en el hígado cirrótico.
3- Determinar el diagnóstico y significado clínico de los nódulos adicionales infracentrimétricos detectados en la fase hepatobiliar.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- more than 18 years old
- patient with diagnosis of liver cirrhosis Child Pugh A-B
- Patients without previous hepatocellular carcinoma in whom ultrasound detects a suspiciuos hepatic lesion; solitary solid and well-defined nodule between 10 and 20 mm
- patients in whom diagnosis of hepatocellular carcinoma is a clinical need prior to treatment indication
- patient that agree to parcicipate signing informed consent form

- Paciente mayor de 18 años.
- Paciente con diagnóstico de cirrosis hepática Child Pugh A-B
- Paciente sin antecedentes de CHC en el que se ha detectado a través de ecografía un único nódulo sólido y bien definido de tamaño superior a 10 mm y menor o igual a 20 mm
- Paciente susceptible de ser tratado tras la detección de un nódulo de CHC
- Paciente que otorga su Consentimiento informado por escrito.

E.4

Principal exclusion criteria

-Patients with poor liver function who would have undergone transplantation even without hepatocellular carcinoma diagnosis (Child-Pugh C)
- patients with previous diagnosis of hepatocellular carcinoma
-patients with significant comorbilities that could prevent the optimum therapeutic decision in case of positive diagnosis of hepatocellular carcinoma
-patients with severe clotting alterations that contraindicate the fine-needle biopsy
-Patients with chronic kidney disease or glomerular filtration rate < 30 ml/min
- patients with contraindications to perform magnetic resonance imaging (pacemaker, claustrophobia...)
- Known hypersensitivity to study drugs or excipients
- pregnancy or breastfeeding

- Pacientes con una función hepática deteriorada, cuya indicación terapéutica sería el trasplante hepático, incluso en ausencia de un CHC concomitante (Child-Pugh C)
- Pacientes con antecedentes de CHC
- Pacientes con comorbilidades que pudieran impedir una decisión terapéutica óptima en el caso de que fueran diagnosticados de un CHC
- Pacientes con severos trastornos de la coagulación que pudieran contraindicar la realización de una PAF
- Pacientes con insuficiencia renal crónica o con un filtrado glomerular <30 ml/min
- Pacientes en los que la obtención de un estudio de RM esté contraindicado (pacientes con marcapasos, claustrofobia?)
- Hipersensibilidad conocida a los medicamentos en estudio o a alguno de sus excipientes.
- Embarazo o lactancia

E.5 End points

E.5.1

Primary end point(s)

Proportion of hepatocellular carcinoma diagnosed using gadoxetic acid magnetic resonance imaging (accuracy for diagnosis)

Proporción de diagnóstico de carcinoma hepatocelular a través de resonancia magnética usando ácido gadoxético como contraste (precisión diagnóstica)

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month

1 mes

E.5.2

Secondary end point(s)

- magnetic resonance imaging sensitivity
- number of patients that need fine-needle biopsy to the diagnosis

- sensibilidad de la resonancia magnética
- número de pacientes que requieren punción con aguja fina para la realización de una biopsia confirmatoria de diagnóstico

E.5.2.1

Timepoint(s) of evaluation of this end point

at the end of the study

a la finalización del estudio

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

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

last vist of last patient

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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)

N/A

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

2012-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-27

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

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