An Ascending Dose Comparison of MVT-100 to Definity in Healthy Volunteers

Sponsor

Microvascular Therapeutics, LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03882359

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), University of Nebraska (Other)

Enrollment

Locations

Arms

29.2

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Definity (perflutren lipid microspheres, Lantheus Medical Imaging) is an ultrasound contrast indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. MVT-100 (the investigational pharmaceutical) is similar to Definity, with the exception of the removal of one lipid in the lipid blend and substitution of another lipid. This study is intended to evaluate the safety and efficacy of MVT-100 using a single ascending dose design in healthy volunteers. Patients are randomized to receive either MVT-100 or Definity and undergo echocardiograms after receiving either MVT-100 or Definity via bolus or IV infusion administration. The primary endpoints evaluated are safety and endocardial border delineation.

Condition or Disease	Intervention/Treatment	Phase
Heart Diseases	Diagnostic Test: Echocardiogram Drug: MVT-100 Drug: Definity	Phase 1/Phase 2

Detailed Description

Ultrasound is one of the most common imaging examinations and has advantages of absence of ionizing radiation, portability and relatively low cost. Ultrasound contrast agents are used to improve the accuracy of ultrasound and Definity (perflutren) is the world's leading ultrasound contrast agent but perflutren has to be refrigerated and has a side effect of back pain. The investigators have developed a new, improved perflutren, MVT-100, with potential for room temperature storage.

Ultrasound contrast agents are used to increase the backscatter (signal intensity of blood vessels and tissues to improve diagnostic accuracy) of ultrasound imaging. In the US ultrasound contrast agents are FDA approved for echocardiography to improve endomyocardial border definition.

MVT-100 reflects the ultrasound to provide strong back-scattering. MVT-100 microbubbles resonate with ultrasound to provide strong harmonic signals. MVT-100 microbubbles will cavitate with higher levels of ultrasound and cavitation may be stable or inertial depending upon acoustic parameters and other factors.

The study is a multi centre ascending dose comparison of Definity and MVT-100 for use in echocardiography and will be performed in a sample of healthy volunteers who are randomized to receive either Definity or MVT-100.

This trial will assess safety and evaluate the following imaging metrics:

Determine the optimal dose of MVT-100 by comparing MVT-100 vs Definity in the change from baseline of quantitative left ventricular opacification
Evaluation of qualitative left ventricular opacification (LVO)
Evaluation of endocardial border delineation
Evaluation of endocardial border length
Evaluation of duration of useful contrast

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Ascending dose comparison in healthy volunteersAscending dose comparison in healthy volunteers

Masking:

Single (Outcomes Assessor)

Masking Description:

The interpreter of echocardiograms in the trial is blinded to the drug which was administered, MVT-100 or Definity.

Primary Purpose:

Diagnostic

Official Title:

MVT-100: Advancing the Clinical Use of Perflutren Ultrasound Contrast Agents for Suboptimal Echocardiograms

Actual Study Start Date :

Oct 25, 2019

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Definity Each subject receives 100 uL x 2, 200 uL x 3, 300 uL x 2 or 1 vial of DEFINITY® 100 diluted in 50 mL of NS as follows: Two milliliter bolus over 10 seconds prior to each infusion rate;, then infusions will run for 5 minutes at 60 mL per hour, 5 minutes at 90 mL per hour, 5 minutes at 100 mL per hour and 5 minutes at 120 mL per hour.	Diagnostic Test: Echocardiogram Images will be recorded in parasternal long, short axis, apical four, two, and three chamber views according to the American Society of Echocardiography (ASE) 17 segment model. Each assessment will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2) in each of the pre-specified windows according to the 2014 ASE Sonographer Guidelines. A baseline echocardiogram will be performed prior to the administration of DEFINITY® or MVT-100. Assessments will be made three times, once from 0 - 1 ½ minutes following injection, once between 1 ½ minutes to 3 minutes following IV injection and once from 3 - 4 ½ minutes following IV injection. Assessments at each time point will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2). Each round will include the views in the following order: parasternal long, parasternal short, apical 4, apical 2 and apical 3. Drug: Definity After randomization, Definity, the active comparator, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.
Experimental: MVT-100 Each subject receives 100 uL x 2, 200 uL x 3, 300 uL x 2 or 1 vial of MVT-100 diluted in 50 mL of NS as follows: Two milliliter bolus over 10 seconds prior to each infusion rate;, then infusions will run for 5 minutes at 60 mL per hour, 5 minutes at 90 mL per hour, 5 minutes at 100 mL per hour and 5 minutes at 120 mL per hour.	Diagnostic Test: Echocardiogram Images will be recorded in parasternal long, short axis, apical four, two, and three chamber views according to the American Society of Echocardiography (ASE) 17 segment model. Each assessment will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2) in each of the pre-specified windows according to the 2014 ASE Sonographer Guidelines. A baseline echocardiogram will be performed prior to the administration of DEFINITY® or MVT-100. Assessments will be made three times, once from 0 - 1 ½ minutes following injection, once between 1 ½ minutes to 3 minutes following IV injection and once from 3 - 4 ½ minutes following IV injection. Assessments at each time point will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2). Each round will include the views in the following order: parasternal long, parasternal short, apical 4, apical 2 and apical 3. Drug: MVT-100 After randomization, MVT-100, the experimental drug, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.

Arm

Intervention/Treatment

Active Comparator: Definity

Each subject receives 100 uL x 2, 200 uL x 3, 300 uL x 2 or 1 vial of DEFINITY® 100 diluted in 50 mL of NS as follows: Two milliliter bolus over 10 seconds prior to each infusion rate;, then infusions will run for 5 minutes at 60 mL per hour, 5 minutes at 90 mL per hour, 5 minutes at 100 mL per hour and 5 minutes at 120 mL per hour.

Diagnostic Test: Echocardiogram

Images will be recorded in parasternal long, short axis, apical four, two, and three chamber views according to the American Society of Echocardiography (ASE) 17 segment model. Each assessment will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2) in each of the pre-specified windows according to the 2014 ASE Sonographer Guidelines. A baseline echocardiogram will be performed prior to the administration of DEFINITY® or MVT-100. Assessments will be made three times, once from 0 - 1 ½ minutes following injection, once between 1 ½ minutes to 3 minutes following IV injection and once from 3 - 4 ½ minutes following IV injection. Assessments at each time point will include one round of low MI imaging (<0.3) and one round of very low MI imaging (<0.2). Each round will include the views in the following order: parasternal long, parasternal short, apical 4, apical 2 and apical 3.

Drug: Definity

After randomization, Definity, the active comparator, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.

Experimental: MVT-100

Each subject receives 100 uL x 2, 200 uL x 3, 300 uL x 2 or 1 vial of MVT-100 diluted in 50 mL of NS as follows: Two milliliter bolus over 10 seconds prior to each infusion rate;, then infusions will run for 5 minutes at 60 mL per hour, 5 minutes at 90 mL per hour, 5 minutes at 100 mL per hour and 5 minutes at 120 mL per hour.

Diagnostic Test: Echocardiogram

Drug: MVT-100

After randomization, MVT-100, the experimental drug, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.

Outcome Measures

Primary Outcome Measures

QT Interval [Day of study]
The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)
Blood Pressure [Day of study]
The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)
Heart Rate [Day of study]
The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)
Oxygen Saturation [Day of study]
The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)
Other Symptoms [Day of study]
The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)

Secondary Outcome Measures

Left Ventricular Opacification (LVO) [Day of Study]
The null hypothesis for efficacy (H0) will be: MVT-100 is not as effective as DEFINITY®. The alternative hypothesis (HA) for efficacy will be: MVT-100 is equivalently or more effective than DEFINITY®. Specifically, the following hypotheses will be tested: HA: LVO(MVT-100) ≥ LVO(Definity®) HA: SegmentVisualization(MVT-100) ≥ SegmentVisualization(Definity®)
Cardiac Segment Visualization [Day of Study]
The null hypothesis for efficacy (H0) will be: MVT-100 is not as effective as DEFINITY®. The alternative hypothesis (HA) for efficacy will be: MVT-100 is equivalently or more effective than DEFINITY®. Specifically, the following hypotheses will be tested: HA: LVO(MVT-100) ≥ LVO(Definity®) HA: SegmentVisualization(MVT-100) ≥ SegmentVisualization(Definity®)

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adult subjects 19 years of age or older, male or female
Female subjects must no longer have child-bearing potential (>1-year post menopause or surgically sterilized), or must
have a negative urine pregnancy test, and
be using and continue to use for 30 days after the study a medically effective method of contraception
Adequate hematologic, renal and hepatic function, as defined by:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Platelet count ≥ 100 x 109/L
Hemoglobin ≥ 90 g/L
Plasma creatinine< 1.5 x ULN
Total bilirubin within normal limits (< 2.5 x ULN if Gilbert's syndrome)
Aspartate transaminase (AST) and Alanine transaminase (ALT) < 2.5 x ULN
Subject must be willing and able to understand the study and provide written Informed Consent to participate in the study

Exclusion Criteria:

Myocardial infarction within six months prior to enrollment
Unstable angina, NYHA Class II or greater congestive heart failure
EKG evidence of uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six months
Clinically significant Chronic Obstructive Pulmonary Disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously
A history of pulmonary emboli
Known hypersensitivity to perflutren, DEFINITY® or other echo contrast agent
Inability to remain supine for 60 minutes
Oxygen saturation < 95% on room air
History of allergic reaction attributed to compounds of similar chemical composition to MVT-100 or DEFINITY® or soy or egg allergies (see Investigator's Brochure)
Subject has received any investigational drug within thirty (30) days prior to enrollment into the study
Inability to comply with study procedures
Subjects with any medical condition deemed by the investigator to make the subject inappropriate for participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85719
2	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198

Sponsors and Collaborators

Microvascular Therapeutics, LLC
National Heart, Lung, and Blood Institute (NHLBI)
University of Nebraska

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Microvascular Therapeutics, LLC

ClinicalTrials.gov Identifier:

NCT03882359

Other Study ID Numbers:

00029941
1R44HL137447-01A1

First Posted:

Mar 20, 2019

Last Update Posted:

May 14, 2021

Last Verified:

May 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Microvascular Therapeutics, LLC

Additional relevant MeSH terms:

Heart Diseases

Study Results

No Results Posted as of May 14, 2021