A Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography

Study Overview
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Brief Summary
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NH002 (Perflutren Lipid Microspheres) Injectable Suspension is an ultrasound contrast agent for use in patients with suboptimal echocardiograms to opacify the left ventricular (LV) chamber and to improve the delineation of the LV endocardial border. The primary objective of this study is to evaluate the safety and tolerability of 3 ascending doses of NH002.

Official Title
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A Multicenter, Open-Label, Dose Ascending Study to Evaluate the Safety of NH002 as a Contrast Agent in Cardiac Echocardiography

Conditions
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Cardiac Disease

Intervention / Treatment
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* Drug: NH002 (Perflutren Lipid Microspheres) Injectable Suspension
* Diagnostic Test: Echocardiogram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 20 years of age or older Ability to understand and the willingness to provide written informed consent Suspected of having cardiac disease or undergoing evaluation of cardiac anatomy for congenital heart disease Negative pregnancy test within 24 hours of the procedure if subject is a woman of childbearing potential Exclusion Criteria: Known right-to-left, bidirectional, or transient right-to-left cardiac shunt(s) Chronic obstructive pulmonary disease Ejection fraction at screening or baseline <40% Uncontrolled serious ventricular arrhythmias or at high risk for arrhythmias due to prolongation of the QT interval (QT corrected by Fridericia's formula >450 msec in males and >470 msec in females) Clinically significant abnormality in renal and liver function tests (alanine aminotransferase/aspartate aminotransferase >2 × upper limit of normal [ULN]; serum creatinine > 1.5 × ULN) Known or suspected hypersensitivity to one or more of the ingredients of NH002, perflutren, or other echocardiographic contrast agent Received an investigational compound within 30 days before enrolling in the study Received any contrast agent either intravascularly or orally within 48 hours before NH002 administration Pregnant or lactating female (conception during the study should be avoided) Serious medical or psychiatric illness/condition likely, in the judgment of the investigator, to interfere with compliance to protocol treatment/research Clinically unstable cardiopulmonary conditions considered not suitable for participation in the trial, in the judgment of the investigator Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Subjects will be enrolled with sequential allocation to 1 of 3 cohorts with the following intravenous (IV) doses of NH002: 2.5 µl/kg, 5.0 µl/kg, or 10.0 µl/kg. Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day | Drug: NH002 (Perflutren Lipid Microspheres) Injectable Suspension<br>* NH002 is formulated as a microbubble injectable suspension for intravenous administration. NH002 requires an activation process prior to use.<br>Diagnostic Test: Echocardiogram<br>* Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-lead ECGs | Standard 12-lead ECGs will be assessed from pre-injection to 60 minutes post-injection for changes in QT/ corrected QT(QTc) interval (in ms) and ECG morphology; each standard 12-lead ECG assessment will be scored as either normal or abnormal | From pre-injection to 60 minutes post injection | 
| Body temperature | Monitor for any changes in body temperature (in Celsius degree) | From pre-injection to 120 minutes post injection | 
| Heart rate | Monitor for any changes in heart rate (in beats/min) | From pre-injection to 120 minutes post injection | 
| Respiratory rate | Monitor for any changes in respiratory rate (in breaths/min) | From pre-injection to 120 minutes post injection | 
| Blood pressure | Monitor for any changes in blood pressure (in mmHg) | From pre-injection to 120 minutes post injection | 
| Thrombin time (TT) and Activated partial thromboplastin time (aPTT) | Monitor for any changes in TT and aPTT | From pre-injection to 240 minutes post-injection | 
| Cardiac troponin I | Monitor for any changes in Cardiac troponin I | pre-injection and 240 minutes post-injection | 
| Oxygen saturation by pulse oximetry (SpO2) | Monitor for any changes in SpO2 | From pre-injection to 120 minutes post-injection | 
| Rate of any potential adverse allergic reaction | Monitor for any potential adverse allergic reaction | From pre-injection to 240 minutes post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Opacification (LVO) | The percentage of subjects with moderate or complete left ventricular opacification (LVO), defined by an LVO grade of 2 (moderate) or 3 (complete), as assessed by the blinded central reader(s). The percentage of subjects with complete LVO, defined by an LVO grade of 3 (complete), as assessed by the blinded central reader(s) | Image data obtained pre-injection and within 10 minutes post-injection | 
| Left Ventricular Endocardial Border Delineation (LVEBD) | The change from baseline on the left ventricular endocardial border delineation (LVEBD) score, defined using a standard 12-segment model, as assessed by the blinded central reader(s). The left ventricular (LV) endocardium of the 4- or 2- chamber apical views are divided into 6 segments, with 2 basal, mid- and apical segments in each view. For each segment, LVEBD is graded as follows: 0= inadequate border (border not visible); 1= sufficient (border barely visible); 2= good (border clearly visible). A total delineation score (0-24) is obtained by adding the scores from the 6 individual segments in each of the 2 views. The changes from baseline on LVEBD score of subjects with suboptimal LVEBD at baseline, as defined by 2 or more contiguous segments of 6 segments that cannot be visualized reliably in either the apical 4 and/or the 2-chamber view, as assessed by the blinded central reader(s) | Image data obtained pre-injection and within 10 minutes post-injection | 
| Duration of clinically useful contrast | A duration of clinically useful contrast calculated by measuring the time between the disappearance of shadowing effect (useful effect starts) and the time when moderate or full LV enhancement and contrast enhancement are no longer adequate (useful effect ends), as assessed by the blinded central reader(s) | Image data obtained pre-injection and within 10 minutes post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Echo, Echocardiogram, Cardiac ultrasound, suboptimal, contrast agent, enhancing agent, LVO, LVEBD