Evaluation of Fontan-Associated Liver Disease (FALD)

Imaging and Biomarker Evaluation of Hepatic Stiffness in Children Enrolled in the Fontan Udenafil Exercise Longitudinal Study

A study to evaluate the efficacy of MZ101 therapy in reducing liver stiffness.

Study Overview

• Status: Unknown
• Conditions: Single Ventricle Heart Disease
• Intervention / Treatment: Drug: MZ101

Detailed Description

This is open-label, long-term prospective study in a cohort of Fontan subjects taking drug daily for one year. The study will determine the scope of hepatic stiffness in the cohort by ultrasound and magnetic resonance imaging elastography and evaluate MZ101 pharmacotherapy as a potentially efficacious treatment to reduce liver stiffness.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 1X8
      • The Hospital for Sick Children
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Cardiac Center/Alfred I. duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20008
      • Children's National Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Kansas
    • Kansas City, Kansas, United States, 64108
      • Children's Mercy Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-4204
      • University of Michigan Congenital Heart Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • University of Nebraska Children's Hospital and Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Medical Hospital/Dept. of Pediatric Cardiology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male and Female subjects 12 - 19 years old with meet the inclusion/exclusion criteria.

Description

Inclusion Criteria:

1. Enrollment in on-going Phase 3 Open-Label Safety Study
2. Informed assent from subject, informed consent from parent/legal guardian as appropriate

Exclusion Criteria:

1. Non-enrollment in the on-going Phase 3 Open-Label Study
2. Subjects with contra-indications for MRI (these subjects will be excluded from the MRI component of this study)
3. Other exclusionary criteria will match those used for the Open-Label Safety Study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MZ101; Dosing per treatment regimen	Drug: MZ101; Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Range of Liver Stiffness in Adolescents with Single Ventricle Heart Disease	Liver Stiffness as measured by Shear Wave Ultrasound Elastography (meters/second) or Magnetic Resonance Ultrasound (kilopascals).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Drug Therapy on Liver Stiffness	Liver Stiffness as measured by Shear Wave Ultrasound Elastography (meters/second) or Magnetic Resonance Ultrasound (kilopascals).	12 months
Effect of Drug Therapy on Brain Type Natriuretic Peptide (BNP) Levels	Measurement of plasma levels of BNP	12 months
Effect of Drug Therapy on n-Terminal BNP (NT-proBNP)	Measurement of plasma levels of NT-proBNP	12 months
Effect of Drug Therapy on MicroRNA Measures.	Measurement of MicroRNA by miRNA qRT-PCR analysis of total RNA from plasma	12 months
Effect of Drug Therapy on Enhanced Liver Fibrosis (ELF) Score	Measurement of ELF Score	12 months

Collaborators and Investigators

• Sponsor: Mezzion Pharma Co. Ltd
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: David J Goldberg, MD, Children's Hospital of Philadelphia; Principal Investigator: Kurt R Schumacher, MD, University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): August 31, 2021

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: February 4, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 22, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Ultrasound; Fontan; Magnetic Resonance Imaging Elastography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Univentricular Heart
• Other Study ID Numbers: PHN-Udenafil-04; U01HL068270 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No