E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Contrast-enhanced MRI in children 2 month to < 2 years
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028049 |
E.1.2 | Term | MRI |
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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 |
Stage 1: To determine the optimal efficacious dose (0.05 mmol/kg or 0.1 mmol/kg BW) of Magnevist Injection
Stage 2: To evaluate pharmacokinetics of Magnevist Injection at the optimal efficacious dose from stage 1 |
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E.2.2 | Secondary objectives of the trial |
Stage 1: To evaluate pharmacokinetics, safety and efficacy of Magnevist Injection Efficacy evaluation by the blinded readers and the open-label investigators
Stage 2: To evaluate the safety and efficacy of Magnevist Injection at the optimal efficacious dose Efficacy evaluation by the blinded readers and the open-label investigators |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must meet all of the following criteria in order to participate in this study:
1. Is at least 2 month but less than 2 years of age 2. Is scheduled to undergo routine Gd-enhanced MRI 3. Signed and dated written informed consent of the legal representative(s) 4. Is able to comply with the study procedures (e.g. will be able for 8 hours after the MRI examination and for follow-up at 24 [+/- 6] hours after the administration of Magnevist Injection) 5. Is able to provide contact information for at least 30 days post-injection for a follow-up phone call |
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E.4 | Principal exclusion criteria |
A subject who meets any of the following criteria shall not participate in this study:
1. Is considered to be clinically unstable (i.e., the underlying clinical condition is such that clinically relevant changes in clinical condition can reasonably be anticipated during the study period). Examples include subjects in intensive care and polytrauma subjects. 2. Has undergone chemotherapy ≤ 48 hours prior to or is scheduled for chemotherapy up to 24 hours after administration of Magnevist Injection 3. Is scheduled for any intervention post-baseline evaluations and up to 24 hours after administration of Magnevist Injection 4. Has participated in a clinical trial of an investigational drug within 30 days prior to consideration for participation in this trial 5. Has received any other contrast agent within 30 hours prior to injection of Magnevist Injection or is likely to receive one during the 24-hour follow-up period 6. Has a contraindication for MRI (e.g. pacemaker, aneurysm clips) 7. Has a history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents 8. Is known to have renal insufficiency (i.e. GFR < 80% of age-adjusted normal value) 9. Has known and clinically relevant (e.g. more than 2 times upper limit of reference range) deviations of available clinical laboratory parameters from reference ranges 10. Previous participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Stage 1: Efficacy: The images obtained post 0.05 mmol/kg BW Magnevist Injection will be compared by the blinded readers to the images obtained post cumulative dose 0.1 mmol/kg BW Magnevist Injection to determine which image set is "superior for diagnosis". The dose considered superior by at least 2 of the 3 blinded readers in at least 8 of the 15 subjects (or majority) will be established as the optimal efficacious dose. Stage 2: PK parameters in plasma: CL, AUC, Vss, t1/2; assessment by non-linear mixed effect modeling. |
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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 | Yes |
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) | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
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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Stage 1 of the trial will be terminated based upon the determination from the open-label investigators that, for the first three enrolled (evaluated) subjects in the study, the images obtained after Magnevist Injection at a dose of 0.05 mmol/kg BW failed to provide sufficient diagnostic information. In this case, the optimal efficacious dose will be Magnevist Injection at 0.1 mmol/kg BW. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 |