Efficacy of EVP 1001-1 (SeeMore) in the Assessment of Myocardial Viability in Patients With Cardiovascular Disease

ISCHEMIC CARDIOMYOPATHY Clinical Trial

Official title:

Efficacy of EVP 1001-1 (SeeMore) in the Assessment of Myocardial Viability in Patients With Cardiovascular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01989195
• Other study ID #: 24224
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 12, 2013
• Last updated: November 14, 2013
• Start date: May 2013
• Est. completion date: June 2013

Study information

• Verified date: November 2013
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

We hope to introduce a novel MRI contrast agent with SeeM ore ™ that directly defines viable myocardium. Identifying viable myocardium non-invasively using cardiac MRI is still a moving target and a question we plan to answer more definitively with the SeeMore ™ contrast. Though well tested. in small and large animals and Phase I & II clinical trials, we would like to determine the efficacy of the SeeM ore TM contrast further in a clinical setting.

SeeM ore ™ is a new manganese (Mn)-based intravenous imaging agent being developed to enhance magnetic resonance imaging (MRI). While Mn has long been known to have desirable magnetic and kinetic properties for MRI, use in humans was not initially possible due to cardiovascular depression and electrocardiogram (ECG)changes, including prolongation of PR and QTc intervals, associated with intravenous administration [1-5]. Chelation of Mn, as had been done with gadolinium for use with MRI, provided relevant safety, but sacrificed desirable magnetic and kinetic properties [6]. SeeM ore rM provides Mn in a form that maintains the desired magnetic and kinetic properties while overcoming the cardiovascular toxicity of Mn. SeeM ore rM is taken up into heart cells .(primarily via addition of calcium to avoid cardiotoxic effects; please refer to US patent #5,980,863). The potential to distinguish healthy heart tissue from unhealthy heart tissue based on a specific sustained pattern of enhancement provides a basis for evaluating the performance of SeeM ore rM in heart patients. MRI offers benefits over other imaging technologies. Relative to radioactive nuclear imaging procedures, MRI is 3-dimensional, provides good soft tissue discrimination, and is of high spatial and temporal resolution. These features have been reported to identify smaller defects (e.g., subendocardial infarcts) and match angiographic results more closely than other modalities such as SPECT [7,8]. It may be possible to enhance the utility of MRI for heart disease further through the use of an imaging agent that is specifically taken up into heart cells. SeeM ore rM is the only cardiac-specific agent being developed for this purpose. Unlike nuclear perfusion agents, SeeM ore rM is not radioactive and does not require special handling, shielding, transport or storage. In addition, the specific pattern of enhancement achieved in the heart muscle persists over time, offering potential .benefits over the nonspecific extracellular agents currently available for MRI or X-ray/CT procedures. This feature allows full use of the high resolution of MRI, since there is not a trade-off of high spatial resolution for temporal (first-pass) resolution. It is anticipated the features offered by SeeMore™ along with the high resolution, three dimensional attributes of MRI will result in higher accuracy than is available with other current modalities in practice, including stress echocardiograms, cardiac MRI using gadolinium contrast and nuclear studies such as SPECT and PET. This will be evaluated in this study and serve as the basis for pivotal registration studies.

All components of SeeMore™ are USP and are approved for use as drugs in man, orally and/or intravenously. A summary of the Phase I safety and PK (pharmacokinetics)study are provided below.

The Phase I study evaluated the safety and tolerance of SeeM ore ™ in humans, with special emphasis on cardiovascular safety, and assessed its PK profile.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

All subjects to be entered must:

• be at least 18 years of age.

• if female, be nonpregnant as evidenced by a serum pregnancy test and using a medically-approved method of birth control, or post-menopausal or surgically sterile

• provide written informed consent after having received oral and written information about the study

• be in stable health based on medical history, examination and tests

Exclusion Criteria:

• have a positive pregnancy test (females)

• received an investigational drug or device within 30 days prior to administration of SeeMore?

• have known hypersensitivity to ondansetron or other selective serotonin 5HT3 receptor blockers

• have a history of drug abuse or alcoholism

• are taking a digitalis preparation or calcium channel blocker

• have a history of torsades or prolonged QT/QTc interval

• have NYHA Grade IV heart failure

• have abnormal liver function tests or a history of liver disease

• have uncontrolled hypertension (Systolic Blood Pressure > 140 or Diastolic BP > 90 consistently at baseline)

• have abnormal baseline potassium or calcium values or hemoglobin less than 10 g/dl

• are noncompliant or otherwise unlikely to perform as required by the protocol

• have pretest likelihood of CAD for which the requisite number of subjects have been entered

• develop an arrhythmia prior to or during either of the exercise tests; SeeMore? should not be administered.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiovascular Diseases
• ISCHEMIC CARDIOMYOPATHY

Intervention

Drug:
• 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT
EACH SUBJECT UNDERWENT 2 CARDIAC MRI PROCEDURES: ONE WITH MAGNEVIST (GADOLINIUM), ONE WITH SEEMORE (MANGANESE) REAGENT CARDIAC MRI USING STANDARD DOSE OF 0.2mMOL/KG MAGNEVIST IV (IN THE VEIN) CARDIAC MRI USING SEEMORE REAGENT, DOSE: 0.35CC/KG IV (IN THE VEIN) 1 WEEK AFTER GADOLINIUM MRI

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COMPARISON OF MYOCARDIAL INFARCTION SIZE MEASUREMENTS USING INVESTIGATIONAL MANGANESE-ENHANCED MRI OR DELAYED GADOLINIUM ENHANCED MRI, AND CORRELATION WITH LONG-TERM OUTCOMES	AFTER INITIAL MRI ACQUISITION, FOLLOW-UP SUBJECT DATA WILL BE ACQUIRED FOR INFORMATION REGARDING MYOCARDIAL INFARCTION, HOSPITALIZATION AND PROCEDURES FOR CHEST PAIN, ARRHYTHMIAS, AND ALL-CAUSE MORTALITY	3 YEAR FOLLOW-UP AFTER INITIAL IMAGING TESTING	No
Primary	Evidence of clinically definite ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI		Within the first 30 days (plus or minus 3 days) after surgery	Yes
Secondary	SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT	SUBJECTS UNDERWENT PRE- AND POST-MRI LABORATORY AND EKG TESTING, AS WELL AS SURVEYS TO ASSESS ANY ADVERSE SYMPTOMS OR SIGNS	Starts pre-MRI with baseline labs and ends one week after manganese delivery. Labs are checked at that timepoint and that completes the safety assessment	Yes