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

NCT01989195 | Completed Phase 1 Results DMC

• 1 other identifier: 24224
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator hopes to introduce a novel MRI contrast agent with SeeMore ™ 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, the investigators would like to determine the efficacy of the SeeMore contrast further in a clinical setting. SeeMore 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 \[1-5\]. SeeMore provides Mn in a form that maintains the desired magnetic and kinetic properties while overcoming the cardiovascular toxicity of Mn. SeeMore 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 SeeMore in heart patients. It may be possible to enhance the utility of MRI for heart disease through the use of an imaging agent that is specifically taken up into heart cells. SeeMore is the only cardiac-specific agent being developed for this purpose. Unlike nuclear perfusion agents, SeeMore 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.

Conditions

ISCHEMIC CARDIOMYOPATHY

Keywords

ISCHEMIC OR CORONARY HEART DISEASE; MYOCARDIAL INFARCTION; MAGNETIC RESONANCE IMAGING; DELAYED GADOLINIUM ENHANCEMENT MRI; MANGANESE-ENHANCED MRI; INFARCT VOLUME/SIZE; ALL CAUSE MORTALITY; VENTRICULAR ARRHYTHMIAS

Outcome Measures

Primary Outcomes (1)

• COMPARISON OF MYOCARDIAL INFARCTION SIZE MEASUREMENTS USING INVESTIGATIONAL MANGANESE-ENHANCED MRI (MEMRI) OR DELAYED GADOLINIUM ENHANCED MRI (DEMRI)

  Measured as percentage of myocardial injury volume to the total left ventricular myocardial volume

  Day 1 (1 MRI)

Secondary Outcomes (3)

• SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT

  Pre MRI and Post MRI on same day (Day 1)

• Significant Cardiovascular Event

  1 year

• Heart Rate: SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT

  Pre MRI and Post MRI on same day (Day 1)

Study Arms (1)

CORONARY DISEASE SUBJECT

EXPERIMENTAL

ALL SUBJECTS IN THIS STUDY HAVE PREVIOUSLY DOCUMENTED CORONARY ARTERY DISEASE BY ANGIOGRAPHY

Drug: 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT

Interventions

'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT DRUG

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

CORONARY DISEASE SUBJECT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Phillip C. Yang, MD
• Organization: Stanford University

phillip@stanford.edu

650-498-8008

Study Officials

• Phillip C. Yang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 20, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: January 2, 2017
• Results First Posted: January 2, 2017

Record last verified: 2016-11

Locations

US (1)