Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy

Phase 2

Recruiting

• Conditions: Duchenne Muscular Dystrophy Cardiomyopathy; Cardiomyopathy, Dilated
• Interventions: Drug: Ifetroban; Drug: Placebo

• Registration Number: NCT03340675
• Lead Sponsor: Cumberland Pharmaceuticals

Brief Summary

Duchenne muscular dystrophy (DMD) is a devastating X-linked disease which leads to loss of ambulation between ages 7 and 13, respiratory failure and cardiomyopathy (CM) at any age, and inevitably premature death of affected young men in their late twenties. DMD is the most common fatal genetic disorder diagnosed in childhood. It affects approximately 1 in every 3,500 live male births across all races and cultures, and results in 20,000 new cases each year worldwide.Significant advances in respiratory care have unmasked CM as the leading cause of death. As there are yet no specific cardiac treatments to extend life, the current study aims to address this unmet medical need using a new therapeutic strategy for patients with DMD.

Funding Source - FDA OOPD

Detailed Description

This is a phase 2 randomized, double-blind, placebo-controlled, multiple dose study with an optional open-label extension to determine the safety, pharmacokinetics (PK) and efficacy of two doses of oral ifetroban in subjects with DMD. DMD patients who meet the inclusion criteria and none of the exclusion criteria will receive oral ifetroban or placebo once daily for 12 months. Subjects will be enrolled onto one of three treatment groups, low-dose ifetroban, high-dose ifetroban or placebo. Each dose level will be evaluated by eight subjects with early stage (LVEF \> 45%) DMD-associated cardiomyopathy and eight subjects with more advanced stage (LVEF 35-45%) cardiac disease as there may be differences in the treatment effect based on cardiac involvement. Each subject treated will be evaluated for first-dose and steady-state exposure PK. All subjects who receive treatment will be assessed for safety. All subjects with at least one efficacy assessment post-baseline will be evaluated for efficacy. Blood and urine will be collected for standard and novel cardiac biomarkers. Target enrollment met for early-stage subjects (LVEF \> 45%) and cohort is closed; enrollment remains open for the late-stage cohort (LVEF 35-45%).

Study Timeline

• Study First Submitted: 2017-11-03
• Study First Submitted QC: 2017-11-08
• Study First Posted: 2017-11-13
• Study Start: 2020-10-19
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-23
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 48

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Ifetroban - High Dose	Ifetroban	Weight based, once daily oral ifetroban
Placebos	Placebo	Matching Placebo
Oral Ifetroban - Low Dose	Ifetroban	Weight based, once daily oral ifetroban

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events (safety & tolerability)	Baseline through 12 months	Percentage of subjects with one or more treatment emergent adverse event

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics time to reach Cmax (Tmax) concentration	Day 0 and Day 7	Measurement of time to reach Cmax (Tmax) concentration of ifetroban and its acyl glucuronide metabolite
Pharmacokinetics plasma terminal half-life concentration	Day 0 and Day 7	Measurement of plasma terminal half-life concentration of ifetroban and its acyl glucuronide metabolite
Change from baseline in left ventricular ejection fraction	Baseline through 12 months	There should be no change in left ventricular ejection fraction. Patients with DMD have a decline.
Pharmacokinetics Area under the curve	Day 0 and Day 7	Measurements of Area under the curve concentration of ifetroban and its acyl glucuronide metabolite
Pharmacokinetics maximum serum concentration (Cmax)	Day 0 and Day 7	Measurements of maximum serum concentration (Cmax) of ifetroban and its acyl glucuronide metabolite
Change from baseline in pulmonary function	Baseline through 12 months	Change from baseline in forced expiratory volume in 1 second
Change from baseline in quality-of-life	Baseline through 12 months	The 23 items Pediatric Quality of Life Inventory (PedQL) questionnaire measures these core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. Items measured include 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). Each item is measured on a 5 point Likert scale with 0 indicating never and 4 indicating almost always.The Likert scores are reversed scored and linearly transform to a 0-100 scale with 0=100, 1-75, 2=50, 5=25, and 4=0. A higher score indicates better health-related quality of life.

Trial Locations

Locations (10)

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Mattel Children's Hospital; 🇺🇸 Los Angeles, California, United States

Children's National Hospital; 🇺🇸 Washington, District of Columbia, United States

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

Lurie Children's Hospital; 🇺🇸 Chicago, Illinois, United States

Riley Children's Hospital; 🇺🇸 Indianapolis, Indiana, United States

Kennedy Krieger Institute; 🇺🇸 Baltimore, Maryland, United States

Saint. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States

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

Monroe Carrell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States