Fontan Udenafil Exercise Longitudinal Assessment Trial - 2

Single Ventricle Heart Disease Clinical Trial

— FUEL-2  

Official title:

Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05918211
• Other study ID #: MZ_Udenafil-05
• Status: Recruiting
• Phase: Phase 3
• Start date: October 30, 2023
• Est. completion date: October 28, 2025

Study information

• Verified date: February 2024
• Source: Mezzion Pharma Co. Ltd
• Contact: John Hariadi, MD
• Phone: 443.699.6746
• Email: john.hariadi[@]mezzion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the clinical efficacy and safety of udenafil, an orally administered, potent and selective inhibitor of PDE5, versus placebo for the treatment of adolescent who have had the Fontan procedure.

Description:

This study is a 26 week, prospective, multicenter, randomized, double-blinded, placebo-controlled safety and efficacy study of udenafil vs. placebo in adolescent subjects who have had the Fontan procedure. The primary efficacy endpoint will be change from baseline at 26 weeks in peak minute oxygen consumption (VO2 mL/kg/min) as measured by maximal cardiopulmonary exercise test (CPET) reading laboratory who will be blinded to treatment allocation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 436
• Est. completion date: October 28, 2025
• Est. primary completion date: October 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment.

2. Participant consent or parental/guardian consent and participant assent.

3. Participant fluency in primary language of country in which study is being conducted.

4. Current antiplatelet or anticoagulant therapy.

Exclusion Criteria:

1. Height < 132 cm.

2. Hospitalization for acute decompensated heart failure within the last 12 months.

3. Current intravenous inotropic drugs.

4. Undergoing evaluation for heart transplantation or listed for transplantation.

5. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis.

6. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of > 4 mmHg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography, obtained prior to screening for the trial.

7. Single lung physiology with greater than 80% flow to one lung.

8. Peak minute oxygen consumption (VO2) less than 45% or = 80% of predicated for age and gender at enrollment.

9. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within 6 months prior to enrollment.

10. Severe valvar regurgitation, ventricular outflow obstruction, or severe aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.

11. History of significant renal (serum creatinine > 2.0), hepatic (serum AST and/or ALT > 3 times upper limit of normal), gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.

12. Inability to complete exercise testing at baseline screening.

13. History of PDE-5 inhibitor use within 12 months prior to enrollment.

14. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.

15. Known intolerance to oral udenafil.

16. Frequent use of medications or other substances that inhibit or induce CYP3A4.

17. Current use of alpha-blockers or nitrates.

18. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.

19. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.

20. Cardiac care, ongoing or planned, at a non-study center that would impede study completion.

21. For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration if sexually active.

22. Unable to abstain or limit intake of grapefruit juice and grapefruit containing drinks during the duration of the trial.

23. Refusal to provide written informed consent/assent.

24. In the opinion of the investigator, the subject is likely to be non-compliant with the study protocol.

25. History of clinically significant thromboembolic event, in the option of the site Principal Investigator, that may put the subject at increased risk of a subsequent event while participating in the study.

26. Coronavirus disease 2019 (COVID-19) vaccination or symptoms of COVID-19 infection within 7 days of Visit 1.

27. Not taking antiplatelet or anticoagulant therapy.

Related Conditions & MeSH terms

• Heart Diseases
• Single Ventricle Heart Disease
• Univentricular Heart

Intervention

Drug:
• Udenafil
Active drug
• Placebo
Matching Placebo

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Hospital of Georgia	Augusta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	MUSC Pediatric Research Group	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Children's Hospital of Colorado	Denver	Colorado
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Mercy Hospital Kansas City	Kansas City	Missouri
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	New York-Presbyterian Children's Hospital	New York	New York
United States	University of Nebraska Children's Hospital and Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Mezzion Pharma Co. Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Exercise Capacity	The change in exercise capacity (as measured by maximal VO2 at maximum exercise effort) from baseline to 26 weeks (or study completion)	Baseline to 26 Weeks
Secondary	Change in VO2 at the ventilatory anaerobic threshold (VAT)	Change in peak oxygen consumption (VO2) from baseline to Week 26 as measured by maximal central cardiopulmonary exercise test (CPET) reading laboratory.	Baseline to 26 weeks
Secondary	Change in Enhanced Liver Fibrosis (ELF) Score	Change from baseline to Week 26 in the Enhanced Liver Fibrosis (ELF) Score calculated by the change in the following biomarkers: hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of metalloproteinase-1. subjects with scores of <7.7 were assigned to the no or mild fibrosis group; 7.7 to 9.8 to the moderate fibrosis group, and >9.8 to the severe fibrosis group.	Baseline to 26 weeks
Secondary	Work rate (watts) at ventilatory anaerobic threshold (VAT)	Change from baseline to 26 weeks in work rate in watts at the ventilatory anaerobic threshold as measured by the central cardiopulmonary exercise test reading laboratory.	Baseline to 26 weeks
Secondary	Change in ventilatory efficiency (VE/VCO2) at ventilatory anaerobic threshold	Change from baseline to Week 26 in ventilatory efficiency calculated by ventilatory efficiency divided by minute carbon dioxide production at the ventilatory anaerobic threshold (VE/VCO2 at VAT).	Baseline to 26 weeks