E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central nervous (CNS) lesions (brain and spine lesions) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | NERVOUS SYSTEM DISORDERS |
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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 document the superiority of Dotarem as a contrast agent over non contrast enhanced MRI for the evaluation of CNS lesions (brain and spine lesions), and the primary objective is in terms of lesion visualization. |
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E.2.2 | Secondary objectives of the trial |
• Compare Dotarem-enhanced MRI to Magnevist-enhanced MRI for: lesion visualization, the quality of images, the level of diagnostic confidence, the signal intensity, number and location of the lesions. • Demonstrate superiority of Dotarem-enhanced MRI to unenhanced MRI for the level of diagnostic confidence, the quality of images, the level of diagnostic confidence, the signal intensity, number and location of the lesions. • Assess the safety profile of Dotarem compared to Magnevist. • Assess the safety and efficacy of Dotarem in pediatric population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult subject, and pediatric subjects (from aged 2 years) who will be enrolled only in Latin America and/or in the USA. • Having been referred for a contrast-enhanced MRI of the CNS based on the results of a previous imaging procedure • Female patients of childbearing potential must have effective contraception (contraceptive pill or intra-uterine device) or be surgically sterilized or post-menopausal (minimum 12 months amenorrhea), or have a documented negative urine pregnancy test within 24 hours prior to study MRI. • Having consented to participate after being fully informed about the study.
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E.4 | Principal exclusion criteria |
• Having acute or chronic grade IV or V renal insufficiency • Known class III/IV congestive heart failure • Suffering from long QT syndrome. • Unstable health condition or circumstances (e.g. suffering from severe claustrophobia). • Having any contraindications to MRI such as a pace-maker, magnetic material or any other conditions that would preclude proximity to a strong magnetic field. • Known allergy to Gadolinium chelates. • Having received any contrast agent within 3 days prior to study contrast administration, or having been scheduled to receive any contrast agent within 24 hours after the study contrast administration. • Pregnant, breast feeding, or planning to become pregnant during the trial. • Previously participated in this trial. • Having participated within 30 days in another clinical trial involving an investigational drug. • Any condition which, based on the investigator's clinical judgement, would prevent the patient from completing all trial assessments and visits. • Inability or unwillingness to cooperate with the requirements of this trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The three co-primary criteria in terms of lesion visualizations (lesion border delineation, lesion internal morphology and lesion contrast enhancement) will be assessed for the five largest representative lesions detected according to the 3-point scales: 0 = Unevaluable/1 = Seen, but imperfectly/2 = Seen completely/perfectly From each of co-primary endpoints, a patient score will be calculated by adding up all lesion scores within subject. The subject primary assessment will consist of 3 separate scores. The primary outcomes will be assessed by off-site readers. The acceptable criterion for the study is that 2 out of 3 readers simultaneously meet the co-primary endpoints.
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Multicentre, randomized, double-blind, fixed-sequence, comparative |
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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.8.2.3.1 | Comparator description |
Marketed medicinal product (Magnevist) |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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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When all recruited patients are enrolled in the study, this will be the end of trial. However, the last subject once screened before the end of trial will be followed until the last visit of this subject. |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |