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

NCT03882359 | Completed Phase 1 FDA Drug

• 2 other identifiers: 000299411R44HL137447-01A1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Heart Diseases

Keywords

echo; echocardiogram; Healthy Volunteers; Definity

Outcome Measures

Primary Outcomes (5)

• QT Interval

  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®)

  Day of study

• Blood Pressure

  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®)

  Day of study

• Heart Rate

  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®)

  Day of study

• Oxygen Saturation

  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®)

  Day of study

• Other Symptoms

  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®)

  Day of study

Secondary Outcomes (2)

• Left Ventricular Opacification (LVO)

  Day of Study

• Cardiac Segment Visualization

  Day of Study

Study Arms (2)

Definity

ACTIVE COMPARATOR

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; Drug: Definity

MVT-100

EXPERIMENTAL

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

Interventions

Echocardiogram DIAGNOSTIC_TEST

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.

Definity; MVT-100

MVT-100 DRUG

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

MVT-100

Definity DRUG

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

Definity

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (6)

• Smith-Bindman R, Miglioretti DL, Johnson E, Lee C, Feigelson HS, Flynn M, Greenlee RT, Kruger RL, Hornbrook MC, Roblin D, Solberg LI, Vanneman N, Weinmann S, Williams AE. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012 Jun 13;307(22):2400-9. doi: 10.1001/jama.2012.5960.

  PMID: 22692172 BACKGROUND

• Platts DG, Luis SA, Roper D, Burstow D, Call T, Forshaw A, Pascoe R. The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging: results from an Australian multicentre cohort. Heart Lung Circ. 2013 Dec;22(12):996-1002. doi: 10.1016/j.hlc.2013.05.637. Epub 2013 Jun 10.

  PMID: 23764145 BACKGROUND

• Weissman, Neil J., Warren J. Manning, and Brian C. Downey. Contrast echocardiography: clinical applications. Waltham, MA : UpToDate, 2013.

  BACKGROUND

• Lantheus Medical Imaging. Definity Package Insert. Definity Imaging. [Online] http://www.definityimaging.com/pdf/DEFINITY_US_PI_515987-0117.pdf.

  BACKGROUND

• Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007 Sep;20(9):1021-41. doi: 10.1016/j.echo.2007.07.003. No abstract available.

  PMID: 17765820 BACKGROUND

• Porter TR, Abdelmoneim S, Belcik JT, McCulloch ML, Mulvagh SL, Olson JJ, Porcelli C, Tsutsui JM, Wei K. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2014 Aug;27(8):797-810. doi: 10.1016/j.echo.2014.05.011. No abstract available.

  PMID: 25085408 BACKGROUND

MeSH Terms

Conditions

Heart Diseases

Interventions

Echocardiography; perflutren

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The interpreter of echocardiograms in the trial is blinded to the drug which was administered, MVT-100 or Definity.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Ascending dose comparison in healthy volunteers

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: March 20, 2019
• Study Start: April 25, 2019
• Primary Completion: September 30, 2024
• Study Completion: May 6, 2025
• Last Updated: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)