A Phase 2 Proof-of-Concept Clinical Trial to Quantify Myocardial Manganese Uptake Rate by Cardiovascular Magnetic Resonance Imaging Following Mangafodipir Trisodium Administration in Healthy Volunteers and Heart Failure Patients With Preserved Ejection Fraction Caused by Hypertrophic Cardiomyopathy or Cardiac Amyloidosis.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- To quantify the manganese uptake rate after administration of mangafodipir trisodium in all segments of the left ventricular wall.
研究概览
简要总结
More than half of heart failure patients have preserved ejection fraction (HFpEF), a condition caused by increased wall stiffness that impairs proper heart filling. Two types of cardiac fibrosis, replacement fibrosis and interstitial fibrosis, contribute to this stiffening. In addition, altered calcium handling in the cardiomyocytes is relevant. The currently available contrast agents in Magnetic Resonace Imaging (MRI) primarily detect cell loss caused by replacement fibrosis, and measurements of the extracellular volume provide clues about the status of interstitial fibrosis. However, the planned trial aims to utilise mangafodipir trisodium to measure cellular function independent of the impact of fibrosis. This information could be vital for accurate diagnosis, selection and monitoring of therapy. In addition, manganese-enhanced magnetic resonance imaging (MEMRI) may be used as an alternative to examinations with gadolinium-based contrast agents in the future.
详细描述
The trial is an open-label, single centre, Phase 2A, Proof-of-Concept (PoC) trial in adult male and female patients without randomisation.
Overall, up to 42 participants will be enrolled in this trial:
- A run-in phase will include up to 6 participants (healthy volunteers and HFpEF patients regardless of aetiology (HCM, CA).
- The main phase of the trial will include 12 HFpEF with HCM, 12 HFpEF with CA and 12 healthy volunteers.
During a run-in phase up to 6 participants will be enrolled to standardise the trial procedures, especially mangafodipir-enhanced imaging.
The number and sequence of trial visits will be the same for participants of the run-in and the main phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who have given their signed declaration of consent and data protection declaration.
- •Males and females (postmenopausal or surgically sterile females) aged ≥ 18 years and ≤ 90 years
- •HFpEF (= LVEF > 50%) with NYHA (New York Heart Association) class I, II and III and objective evidence of cardial structural and/or functional abnormalities consistent with the presence of left ventricular (LV) diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides.
- •Patients with HCM or CA (according to current guidelines)
- •Kidney functions eGFR (Estimated Glomerular Filtration Rate) > 30 mL/min/1.73 m2
- •Healthy volunteers (cohort specific criteria): adults with no known pre-existing medical conditions.
排除标准
- •Tachycardia (heart rate > 100, R-R interval < 600 ms)
- •Previous coronary artery disease requiring intervention, including history of myocardial infarction including septal reduction therapies
- •Severely reduced renal function, defined as eGFR < 30 mL/min/1.73 m2
- •Severely reduced liver function (Child-Pugh class C), especially severe obstructive hepatobiliary disease
- •Phaeochromocytoma
- •Advanced cancer (with short/medium term prognosis)
- •History of chest radiation therapy
- •Diabetic patients
- •Severe valvular disease
- •Previous heart surgery
- •Left ventricular assist device (LVAD)
- •Severe pulmonary disease
- •Hypersensitivity to any medicinal products containing gadolinium
- •Hypersensitivity to the active substance of the IMP or to any of the excipients
- •Contraindications to MRI, including implanted cardiac devices/pacemakers
- •Participants not able to follow instructions necessary to conduct the MRI
- •Women of childbearing potential
- •Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days
- •Previous participation in this clinical trial
- •History of ongoing drug abuse or alcoholism
- •Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the trial
- •Investigator site staff and sponsor directly involved in the conduct of the study and their family members.
研究组 & 干预措施
HFpEF with HCM
Heart failure patients with preserved ejection fraction caused by hypertrophic cardiomyopathy.
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Gadoteric acid (Drug)
HFpEF with HCM
Heart failure patients with preserved ejection fraction caused by hypertrophic cardiomyopathy.
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Mangafodipir trisodium injection (Drug)
HFpEF with CA
Heart failure patients with preserved ejection fraction caused by cardiac amyloidosis.
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Gadoteric acid (Drug)
HFpEF with CA
Heart failure patients with preserved ejection fraction caused by cardiac amyloidosis.
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Mangafodipir trisodium injection (Drug)
Healthy Volunteers
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Gadoteric acid (Drug)
Healthy Volunteers
Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.
干预措施: Mangafodipir trisodium injection (Drug)
结局指标
主要结局
To quantify the manganese uptake rate after administration of mangafodipir trisodium in all segments of the left ventricular wall.
时间窗: Images to be captured during the trial MRI examinations (up to 60 to 90 minutes after the drug administration); image evaluations shall be executed remotely.
Determination of the manganese uptake rate.
次要结局
- Efficacy: Comparison of manganese uptake rate constant in healthy volunteers, HFpEF with HCM or CA.(Images to be captured during the trial MRI examinations (up to 60 to 90 minutes after the drug administration); image evaluations shall be executed remotely.)
- To assess the safety of mangafodipir trisodium injection based on AEs.(From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).)
- To assess the safety of mangafodipir trisodium injection based on injection site AEs.(From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).)
- To assess the safety of mangafodipir trisodium injection based on vital signs.(From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).)
- To assess the safety of mangafodipir trisodium injection based on ECG.(From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).)