Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness (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: Completed
• Conditions: Single Ventricle Heart Disease
• Intervention / Treatment: Drug: Udenafil

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: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

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 D.C., 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

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

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Udenafil Continuation (U+); Subjects who were receiving Udenafil 87.5 mg BID in FUEL study prior to enrolling to this study (FALD).	Drug: Udenafil; Open-label extension with Udenafil 87.5 mg BID treatment for 52 weeks.
Experimental: Udenafil Naive (U-); Subjects who were receiving Placebo BID in FUEL study prior to enrolling to this study (FALD).	Drug: Udenafil; Open-label extension with Udenafil 87.5 mg BID treatment for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography	Liver stiffness was measured at baseline and 52 weeks using Ultrasound Shear Wave Elastography (USWE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.	52 weeks
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography	Liver stiffness was measured at baseline and 52 weeks using Magnetic Resonance Elastography (MRE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment	Overall ELF score. ELF score is based on the serum levels of hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1), and calculated using the following formula: ELF score= 2.494+0.846 In(CHA)+0.391 In(CPIIINP)+0.391 In(CTIMP-1). The levels of each component were as assessed individually and as part of the calculated ELF score as continuous variables. The normal range in healthy subjects ≤20 years of age is 6.9 - 8.8. Correlations between ELF and the degree of liver fibrosis have not been established in patients with Fontan circulation, however, a decrease in ELF score is associated with improved liver health in other disease states.	52 weeks
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment	Brain Natriuretic Peptide (BNP) was measured at baseline and 52 weeks of treatment. BNP is a biomarker of overall cardiac function across a variety of disease states. A decrease in value is associated with improved cardiac function.	52 weeks

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 (Actual): September 15, 2020
• Study Completion (Actual): September 16, 2020

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 (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Fontan; Magnetic Resonance Imaging Elastography; Ultrasound Shear Wave Elastography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Univentricular Heart; Heart Diseases; udenafil
• 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)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No