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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 60
- 主要终点
- Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Mangoral
All participants will receive a single dose of Mangoral (800 mg Manganese (II) chloride tetrahydrate [MnCl2 4H2O]).
干预措施: Mangoral (Drug)
结局指标
主要结局
Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI
时间窗: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion border delineation from 1 (poor: lesion border is poorly distinct) to 4 (excellent: lesion border is sharply and clearly distinct). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.
Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI
时间窗: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0
Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion contrast from 1 (poor: difference in signal intensity between the lesion and the surrounding normal liver tissue is poor) to 4 (excellent: difference in signal intensity between the lesion and the surrounding liver is marked). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.
次要结局
- Number of Lesions Detected by Each MRI Method(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0)
- Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Confidence in Lesion Detection Score(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0)
- Longest Diameter of Largest and Smallest Lesion(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Confidence in Lesion Localization Score(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0)
- Percentage Liver Signal Intensity (SI) Enhancement in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Liver-to-lesion Contrast (LLC) in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Signal-to-noise Ratio (SNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Contrast-to-noise Ratio (CNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0)
- Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI(Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0)