Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness

Not Applicable

Completed

• Conditions: Single Ventricle Heart Disease
• Interventions: Drug: Udenafil

• Registration Number: NCT03430583
• Lead Sponsor: Mezzion Pharma Co. Ltd

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-01-22
• Study First Submitted QC: 2018-02-04
• Study First Posted: 2018-02-13
• Study Start: 2018-02-20
• Primary Completion: 2020-09-15
• Study Completion: 2020-09-16
• Results First Submitted: 2025-08-24
• Status Verified: 2025-09
• Results First Submitted QC: 2025-09-16
• Results First Posted: 2025-09-18
• Last Update Submitted: 2025-09-24
• Last Update Posted: 2025-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Udenafil Continuation (U+)	Udenafil	Subjects who were receiving Udenafil 87.5 mg BID in FUEL study prior to enrolling to this study (FALD).
Udenafil Naive (U-)	Udenafil	Subjects who were receiving Placebo BID in FUEL study prior to enrolling to this study (FALD).

Primary Outcome Measures

Name	Time	Method
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	52 weeks	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.
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	52 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment	52 weeks	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.
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment	52 weeks	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.

Trial Locations

Locations (17)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Nemours Cardiac Center/Alfred I. duPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Children's National Medical Center; 🇺🇸 Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Kansas, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan Congenital Heart Center; 🇺🇸 Ann Arbor, Michigan, United States

Children's Mercy Hospital Kansas City; 🇺🇸 Kansas City, Missouri, United States

University of Nebraska Children's Hospital and Medical Center; 🇺🇸 Omaha, Nebraska, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

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