Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function

Study Overview
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Brief Summary
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The overall objective of this study is to evaluate the safety and diagnostic efficacy of Mangoral in liver MRI in participants with known or suspected focal liver lesions and severe renal impairment. The diagnostic efficacy of Mangoral will be assessed in terms of visualization of detected focal liver lesions in combined MRI (CMRI: combined Mangoral-enhanced and unenhanced MRI) compared to unenhanced MRI.

Detailed Description
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The overall objective of this multicenter, open-label, study is to evaluate the safety and diagnostic efficacy of Mangoral in participants with known or suspected focal liver lesions and severe renal impairment. Study treatment is a single oral dose of Mangoral (800 mg manganese chloride [II] tetrahydrate, 500 mg L-alanine, and 800 IU vitamin D3). Adult male and female participants with severe renal impairment or acute kidney injury and who are being evaluated for known or suspected focal liver lesions will be included. Primary diagnostic efficacy in terms of visualization of detected lesions will be evaluated centrally by 3 independent readers. Study MRIs will also be evaluated by the on-site radiologists for the assessment of secondary objectives and for clinical purposes.

Official Title
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A Multicenter, Open-label Study to Evaluate the Safety and Diagnostic Efficacy of Mangoral in Patients With Known or Suspected Focal Liver Lesions and Severe Renal Impairment

Conditions
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Known or Suspected Focal Liver Lesions and Severe Renal Impairment

Intervention / Treatment
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* Drug: Mangoral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants 18 years and older. Known or suspected focal liver lesions based on medical history and previous laboratory and/or imaging examinations. Severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m^2) based on medical history and previous laboratory examinations, at least once, within the last 3 months prior to the Baseline Visit, or participants with an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours or ≥ 50% within 7 days prior to the Baseline Visit. Exclusion Criteria: Participants with simple liver cysts only. Any investigational drug or device within 6 weeks prior to the Baseline Visit. Any magnetic resonance imaging (MRI) contrast media within 6 weeks prior to Baseline Visit or scheduled to receive any contrast medium before the last study visit. Participants with severe hepatic impairment (according to Child-Pugh score C). Participants scheduled for surgery before last study visit. Participants with encephalopathy / neurodegenerative or acute neurological disorders. Participants with hemochromatosis.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Multicenter, open-label, pivotal phase III study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mangoral<br>All participants will receive a single dose of Mangoral (equivalent to 800 mg Manganese (II) chloride tetrahydrate [MnCl2 4H2O]). | Drug: Mangoral<br>* 800 mg manganese chloride [II] tetrahydrate, 500 mg L-alanine, and 800 IU vitamin D3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the visualization of detected focal liver lesions in combined MRI (CMRI, Mangoral-enhanced MRI plus unenhanced MRI) as compared to unenhanced MRI. | Visualization will be measured by 2 co-primary variables: lesion border delineation and lesion contrast compared to liver background. Central reading sessions by 3 independent readers for all 3 parts (CMRI, Mangoral-enhanced MRI plus unenhanced MRI). There will be a 2-weeks gap between read parts to reduce recall bias. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of lesions detected by each MRI method (unenhanced MRI, Mangoral-enhanced MRI, and CMRI.) | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Visualization of focal liver lesions in Mangoral-enhanced MRI as compared to unenhanced MRI | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Confidence in lesion detection separately in unenhanced MRI, Mangoral-enhanced MRI, and CMRI | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Confidence in lesion localization separately in unenhanced MRI, Mangoral-enhanced MRI, and CMRI | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Lesion dimensions: longest diameter of largest and smallest lesion | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Quantitative assessments for up to 5 detected lesions (liver signal intensity enhancement; liver-to-lesion contrast; signal-to-noise ratio; contrast-to-noise Ratio) | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year | 
| Change(s) in patients' Management based on diagnostic Performance of CMRI or Mangoral-enhanced MRI vs. unenhanced MRI | Assessments will be done during central reading sessions as described for primary outcome. Additionally on-site evaluation will be done within 5 working days after the respective MRI examination | 1 year |