E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central nervous system (CNS) pathology |
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E.1.1.1 | Medical condition in easily understood language |
Brain and spinal cord conditions |
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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 | 22.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051290 |
E.1.2 | Term | Central nervous system lesion |
E.1.2 | System Organ Class | 10029205 - 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 identify a dose for further development that has an overall diagnostic preference rate similar to that of the comparator gadobutrol at 5 min post injection |
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E.2.2 | Secondary objectives of the trial |
To show non-inferiority of BAY1747846 compared to gadobutrol at 5 min post injection with respect to sum of lesion visualization parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be at least 18 years of age at the time of signing the informed consent. 2. Known or highly suspected CNS pathology (contrast-enhancing CNS lesion) referred for contrast-enhanced MRI of the CNS. 3. Male and female. 4. Estimated glomerular filtration rate (eGFR) value ≥60 mL/min/1.73m^2. |
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E.4 | Principal exclusion criteria |
1. Considered clinically unstable or has a concomitant/intercurrent condition (e.g. COVID-19 infection) that would not allow participation for the full planned study period in the judgement of the investigator. 2. Severe cardiovascular disease. 3. Patients undergoing liver transplantation. 4. Any contraindication to MRI examinations. 5. History of severe allergic or anaphylactic/anaphylactoid reaction to any allergen including drugs and contrast agents, foods, chemicals or other substances. 6. History of allergic asthma and/ or atopic dermatitis. 7. Suspected lesions or suffering from any of the following CNS diseases/lesion types as the main indication for MRI: • Lepto-meningeal disease (e.g. leptomeningeal carcinomatosis). Dural lesions (e.g. meningiomas) fulfilling inclusion criteria #2 are not excluded • Pituitary adenomas (macro and micro) • Tumors of the choroid plexus • Tumors of the pineal gland • Dermoid/epidermoid tumors • Infectious disease (e.g. brain abscess, cisticercosis, etc.) • Venous angiomas • Subacute/chronic ischemia • Encephalitis • Multiple sclerosis (acute and chronic) • Optic neuritis • Chordomas • Von Hippel Lindau syndrome • Hypertensive leukoencephalopathy. 8. Receipt of any contrast agent <72 h prior to the study MRIs, or planned receipt of any contrast agent within 72 h after the second study MRI. 9. Planned or expected biopsy in the region of interest or any interventional therapeutic procedure from the first study MRI up to 24 h after the second study MRI. 10. Planned or expected change in any treatment or procedure between the two study MRIs that may alter image comparability and /or chemotherapy which is changed between the two MRI procedures. 11. Contraindications to the administration of gadobutrol, i.e. history of severe hypersensitivity reaction to gadobutrol (depending on local product label). 12. Has received any investigational product within 30 days, or within 5 times half-life of the investigational product, whichever is shorter, prior to enrolling in this study. Note: Participants who have entered the followup period of or have been discontinued from an investigational study may participate as long as it has been 30 days after the last dose of the previous investigational product, or 5 times half-life of that investigational product, whichever is shorter. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall diagnostic preference |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 5 minute post injection |
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E.5.2 | Secondary end point(s) |
Sum of lesion visualization parameters |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 5 minute post injection |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 | 1 |
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 | 5 |
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 | No |
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 |
Japan |
United States |
Bulgaria |
Germany |
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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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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |