A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children

Study Overview
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Brief Summary
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In this clinical study a contrast agent for magnetic resonance imaging (MRI), which has already been approved for application in adults, will be investigated in children and adolescents. MRI is a modern and safe examination method without delivering radiation burden using magnetic fields to produce cross-sectional images of the human body. A special computer program then puts these images together and creates a two or three-dimensional image of the inner organs thus facilitating the detection and evaluation of pathological changes. In contrast-enhanced MRI a contrast agent is injected into a peripheral vein before the examination which results in a stronger contrast in the examined area. Therefore, pathological changes can be more easily detected and evaluated compared to non-enhanced MRI. The company Bayer HealthCare Pharmaceuticals has developed a contrast agent for MRI called Gadavist 1.0 which was first approved in 1998 in Switzerland for MRI of brain and spine. Since 2003 Gadavist can also be used in magnetic resonance angiography (MRA) in adults, i.e. in the MRI examination of the blood vessels and since 2006 in MRI of liver and kidney disease. Gadavist was examined in more than 2,900 adults within the framework of clinical studies during development and has been used after its marketing authorization in meanwhile more than 600,000 patients. Yet, clinical studies investigating Gadavist have been only conducted with adults so far. Diseases requiring MRI examinations, however, often occur in children, too. Therefore, many contrast agents are already used on a regular basis in MRI examinations of children, some of these contrast agents being authorized already. Within the framework of this study the pharmacokinetic characteristics of Gadavist in children or adolescents will be investigated, i.e. how the contrast agent is distributed and behaves in the body. In addition, safety and tolerability will be evaluated in order to demonstrate that Gadavist 1.0 is a safe and well tolerated contrast agent also for children and adolescents. Furthermore, the study aims to obtain the dosage recommendation of 0.1 ml per kilogram body weight also for this population group.

Detailed Description
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Please note that the present study is allocated two study phases, i.e. phase I and phase III.

Official Title
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Open-label Multi-center Study of Magnetic Resonance Imaging (MRI) With 0.1 mmol/kg Body Weight (BW) Gadavist (1.0 M) to Assess Pharmacokinetics, Safety and Tolerability in Children.

Conditions
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Magnetic Resonance Imaging

Intervention / Treatment
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* Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (male/ female) of specific age groups (2-6 years, 7-11 years, 12-17 years) who are scheduled to undergo Gadolinium (Gd)-enhanced MRI of brain, spine, liver and/or kidneys or Gd-enhanced MRA (single field of view). Exclusion Criteria: Clinically unstable patients (e.g. intensive care unit) Renal insufficiency Patients undergoing a relevant change in chemotherapy </= 48 hours prior to and up to 24 hours after the administration of Gadovist.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 2 to 6 years<br>Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection<br>|
| Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 7 to 11 years<br>Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection<br>|
| Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 12 to 17 years<br>Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection<br>|
| Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 2 to 17 years<br>Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Clearance Estimates of Gadobutrol by Age Group | Total body clearance of Gadobutrol in plasma in L/h after intravenous injection. | From injection of Gadobutrol up to 8 hours after injection. | 
| Body Weight-corrected Plasma Clearance Estimates of Gadobutrol by Age Group | Total body clearance of Gadobutrol in plasma corrected for body weight (L/h/kg) after intravenous injection. | From injection up to 8 hours after Gadobutrol injection | 
| Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group | Apparent volume of distribution at steady state expressed in L after intravenous injection. | From injection up to 8 hours after Gadobutrol injection | 
| Body Weight-corrected Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group | Apparent volume of distribution at steady state corrected for body weight (L/h/kg) after intravenous injection. | From injection to 8 hours after Gadobutrol injection | 
| Area Under the Drug Concentration-time Curve of Gadobutrol by Age Group | Area under the concentration versus time curve from zero to infinity after intravenous injection expressed in µmol*h/L. | From injection to 8 hours after Gadobutrol injection | 
| Terminal Elimination Half Life Estimates of Gadobutrol by Age Group | Terminal elimination half-life of Gadobutrol from plasma expressed in h and derived from the terminal slope of the concentration versus time curve. | From injection to 8 hours after Gadobutrol injection | 
| Mean Residence Time (MRT) Estimates of Gadobutrol by Age Group | Mean residence time of Gadobutrol in plasma expressed in h. | From injection to 8 hours after Gadobutrol injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Excretion of Gadolinium as Percent of Administered Dose | Amount of gadolinium* excreted into urine during the collection interval 0 - 6 h post dose expressed as % of administered dose. *A metallic rare-earth element, used as a contrast medium for magnetic resonance imaging. | up to 6 hours after Gadobutrol injection | 
| Number of Participants With Basic Technical Adequacy of Magnetic Resonance (MR) Images for Diagnosis by Age Group | In the participants the technical adequacy (evaluability) of MR images was assessed on the following 4-point scale (1=not adequate [compromised quality], 2=partially adequate [evaluation possible], 3=adequate despite artifacts, 4=adequate with excellent quality). | Up to 1 hour after Gadobutrol injection | 
| Number of Participants With Overall Contrast Quality of Post Contrast Images by Age Group | In the participants qualitative overall contrast quality of post contrast images was assessed on the following 6-point scale (none, poor, moderate, good, excellent, not assessable). | up to 1 hour after Gadobutrol injection | 
| Pre-Contrast Lesions by Location and by Age Group | Number of lesions on pre-contrast images by organ location and age group. | up to 1 hour after Gadobutrol injection | 
| Post-Contrast Lesions by Location and by Age Group | Number of lesions on post-contrast images by organ location and age group. | up to 1 hour after Gadobutrol injection | 
| Pre-Contrast Delineation of Lesion/Vessel Border by Age Group | In the participants pre-contrast delineation of each lesion/vessel border was assessed on the following 5-point scale (no, moderate, good, excellent, not assessable). | up to 1 hour after Gadobutrol injection | 
| Post-Contrast Delineation of Lesion/Vessel Border by Age Group | In the participants post-contrast delineation of each lesion/vessel border was assessed on the following 5-point scale (no, moderate, good, excellent, not assessable). | up to 1 hour after Gadobutrol injection | 
| Pre-Contrast Lesion Characterization by Age Group | In the participants the internal morphology and structure of each pre-contrast lesion was assessed on the following 4-point scale (1=poor, 2=moderate, 3=good, 4=not applicable). | up to 1 hour after Gadobutrol injection | 
| Post-Contrast Lesion Characterization by Age Group | In the participants the internal morphology and structure of each post-contrast lesion was assessed on the following 4-point scale (1=poor, 2=moderate, 3=good, 4=not applicable). | up to 1 hour after Gadobutrol injection | 
| Degree of Contrast Enhancement in Lesion/Vessel by Age Group (Given Are Total Numbers of Lesions) | In the participants the degree of contrast enhancement in each lesion/vessel was assessed on the following 5-point scale (1=no, 2=moderate, 3=good, 4=excellent, 5=not applicable). | up to 1 hour after Gadobutrol injection | 
| Number of Participants With Change in Diagnostic Confidence by Age Group | In the participants the change in diagnostic confidence (additional diagnostic gain by the post-contrast scan) was assessed on the following 3-point scale (1=unchanged, 2=improved, 3=worsened). | up to 1 hour after Gadobutrol injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contrast-enhanced MRI, MR angiography (MRA) Children 2-17 years