E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Contrast enhancement in magnetic resonance imaging (MRI) for central nervous system (CNS), magnetic resonance (MR) angiography, liver, kidney and other body regions |
Migliormento del contrasto nella la risonanza magnetica (RMI), angiografia con risonanza magnetica [angio-RM], fegato, reni e altre aree del corpo |
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E.1.1.1 | Medical condition in easily understood language |
Enhancement and improvement of the quality of pictures generated during MRI |
Enhancement and improvement of the quality of pictures generated during MRI |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
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 | 10028049 |
E.1.2 | Term | MRI |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate noninferiority of gadobutrol-enhanced CNS imaging (at a dose of 0.075 mmol/kg) compared to gadoterate (0.1 mmol/kg BW) - enhanced CNS imaging (at a dose of 0.1 mmol/kg) for 3 lesion visualization parameters (degree of contrast enhancement, assessment of border delineation, and internal morphology of lesions) based on a blinded read. |
dimostrare la non inferiorità della diagnostica per immagini del SNC evidenziato con gadobutrolo (a una dose di 0,075 mmol/kg) rispetto alla diagnostica per immagini del SNC evidenziato con gadoterato (0,1 mmol/kg di peso corporeo) (a una dose di 0,1 mmol/kg) come mezzi di contrasto per 3 parametri di visualizzazione delle lesioni (livello di marcatura del contrasto, valutazione della delineazione del bordo e morfologia interna delle lesioni) sulla base di una lettura in cieco |
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E.2.2 | Secondary objectives of the trial |
-Demonstrate noninferiority for number of lesions based on a blinded read -Confidence in diagnosis -Confrontare la dose di 0,075 mmol/kg di peso corporeo di gadobutrolo con la dose standard di gadoterato (Dotarem) per: o T1w MRI image quality in a paired blinded comparison o Sensitivity/Specificity for presence of malignant disease based on a blinded read -Compare the overall contrast enhancement of gadobutrol (0.075mmol/kg BW) to the standard dose of gadoterate (0.1 mmol/kg) for steady-state CNS imaging. Quantitative contrast enhancement will be performed using an exploratory Overall Contrast Enhancement Estimation Algorithm. |
• Dimostrare la non inferiorità per numero di lesioni • Sicurezza della diagnosi • Confrontare la dose di 0,075 mmol/kg di peso corporeo di gadobutrolo con la dose standard di gadoterato (Dotarem) per: o Qualità dell’immagine della RMI in T1w in un confronto accoppiato o Sensibilità/specificità per la presenza di tumore maligno rispetto alla diagnosi clinica finale. • Confrontare l’intensificazione contrastografica complessiva di gadobutrolo (0,075 mmol/kg di peso corporeo) con la dose standard di gadoterato 0,1 mmol/kg) per imaging in stato costante del SNC. L’intensificazione contrastografica quantitativa sarà effettuata usando un algoritmo esplorativo di stima dell’intensificazione contrastografica complessiva. • Valutare il profilo di sicurezza della dose ridotta di 0,075 mmol/kg di peso corporeo di gadobutrolo e la dose standard di gadoterato dopo la somministrazione EV |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have known or highly suspected CNS pathology referred for contrast-enhanced MRI of the CNS based on current clinical symptoms or on a previous procedure. 2. If female and of child bearing potential, have a negative urine pregnancy test within 1 hour prior to the administration of gadoterate (the first MRI). 3. Have an estimated glomerular filtration rate (eGFR) value = 60 mL/min/1.73m2 derived from a serum creatinine result within four (4) weeks prior to the first study MRI. 4. Be fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable, and consent to participate |
1. Presentare una patologia del SNC nota o altamente sospetta per cui è stato indirizzato per RMI a intensificazione contrastografica del SNC sulla base di sintomi clinici attuali o di una precedente procedura. 2. Se di sesso femminile e in età fertile, sottoporsi a test di gravidanza sulle urine con risultato negativo entro 1 ora prima della somministrazione di gadoterato (la prima RMI). 3. Presentare un tasso di filtrazione glomerulare stimato (eGFR) di valore = 60 ml/min/1,73m2, derivato da un risultato della creatinina sierica entro quattro (4) settimane prima della prima RMI dello studio. 4. Essere pienamente informato sullo studio, incluse le disposizioni della Legge sulla portabilità e responsabilità dell’assicurazione sanitaria (Health Insurance Portability and Accountability Act, HIPAA) ove pertinente, e avere fornito il consenso a partecipare |
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E.4 | Principal exclusion criteria |
1. Has no enhancing lesion visible on the gadoterate-enhanced MRI scan. 2. Is pregnant or breast feeding 3. Has received any investigational product or has participated in any other clinical trial within 30 days prior to enrolling in this study 4. Has any contraindication to the MRI examinations or the use of gadolinium-containing contrast agents 5. Has a history of severe allergic or anaphylactic/anaphylactoid reaction to any allergen including drugs and contrast agents 6. Has received any gadolinium-based contrast agent < 24 hours prior to the study MRIs, or is scheduled to receive any contrast agent within 24 hours after the second study MRI 7. Is considered clinically unstable 8. Has severe cardiovascular disease (eg, known long QT syndrome, acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association class IV or acute stroke (< 48 hours) 9. Is expected or is scheduled to have a change in any treatment or procedure between the gadoterate and gadobutrol MRIs that may alter image comparability 10. Is scheduled or is likely to require a biopsy or any interventional therapeutic procedure from the first study MRI up to 24 hours after the second study MRI |
1. Non presenta lesione captante visibile alla RMI intensificata con gadoterato. 2. È incinta o sta allattando al seno 3. Ha ricevuto qualsiasi prodotto sperimentale o ha partecipato a qualsiasi altra sperimentazione clinica entro 30 giorni prima dell’arruolamento in questo studio 4. Presenta qualsiasi controindicazione agli esami con RMI o all’uso di agenti di contrasto contenenti gadolinio 5. Presenta un’anamnesi di grave reazione allergica o anafilattica/anafilattoide a qualsiasi allergene inclusi farmaci e agenti di contrasto 6. Ha ricevuto qualsiasi agente di contrasto a base di gadolinio <24 ore prima delle RMI dello studio o prevede di ricevere qualsiasi agente di contrasto entro 24 ore dopo la seconda RMI dello studio 7. È considerato clinicamente instabile 8. Presenta una malattia cardiovascolare grave (ad es. sindrome del QT lungo nota, infarto miocardico acuto [<14 giorni], angina instabile, insufficienza cardiaca congestizia di classe IV secondo la New York Heart Association o ictus acuto (<48 ore) 9. Si prevede, oppure è programmata, una modifica di qualsiasi trattamento o procedura tra le RMI con gadoterato e gadobutrolo che possa alterare la comparabilità delle immagini. 10. È programmata o è probabile che sia necessaria una biopsia o qualsiasi procedura terapeutica interventistica dalla prima RMI dello studio fino a 24 ore dopo la seconda RMI dello studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Lesion visualization parameters based on a blinded read: -degree of contrast enhancement -assessment of border delineation -internal morphology of lesions |
Parametri di visulaizzaione delle lesioni sulla base di una lettura in cieco: -livello di marcatura del contrasto -valutazione della delineazione del bordo -morfologia interna delle lesioni |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Refer to schedule of events |
Refer to schedule of events |
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E.5.2 | Secondary end point(s) |
-Number of lesions identified (up to 10) based on a blinded read -Identification of benign or malignant disease based on blinded read -Confidence in diagnosis based on a blinded read -Image quality based on a blinded read -Contrast enhancement utilizing an exploratory Overall Contrast Enhancement Estimation Algorithm |
-Number of lesions identified (up to 10) based on a blinded read -Identification of benign or malignant disease based on blinded read -Confidence in diagnosis based on a blinded read -Image quality based on a blinded read -Contrast enhancement utilizing an exploratory Overall Contrast Enhancement Estimation Algorithm |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Refer to schedule of events |
Refer to schedule of events |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
France |
Germany |
Italy |
Korea, Republic of |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of the blinded read, approximately 30 days after the LPLV |
The end of the blinded read, approximately 30 days after the LPLV |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |