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

Mezzion Pharma Co. Ltd88 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Single Ventricle Heart Disease

Interventions

UdenafilDRUG

Open-label extension with Udenafil 87.5 mg BID treatment for 52 weeks.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (17)

Children's Hospital Colorado

Aurora, Colorado, United States

Nemours Cardiac Center/Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 52 weeks

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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