Summary

Eligibility
for males ages 7 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study With an Open-Label Extension to Determine the Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy

Details

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.

Keywords

Duchenne Muscular Dystrophy Cardiomyopathy Cardiomyopathy, Dilated Muscular Dystrophies Muscular Dystrophy, Duchenne Cardiomyopathies Ifetroban

Eligibility

You can join if…

Open to males ages 7 years and up

  1. Males 7 years of age and older with the diagnosis of DMD, defined as phenotype consistent with DMD and either positive genotype, first degree relative with positive genotype, or confirmatory muscle biopsy.
  2. Stable dose of oral corticosteroids for at least 8 weeks or has not received corticosteroids for at least 30 days.
  3. Stable cardiac function defined as change in left ventricular ejection fraction (LVEF) of < 15% and no heart failure admission over the last 12 months; LVEF 35% or greater by cine cardiac magnetic resonance imaging (MRI) or echocardiography; myocardial damage in one or more left ventricular segments evident by late gadolinium enhancement allowed; concurrent angiotensin-converting enzyme inhibitors (ACEI), beta-blocker (BB) or angiotensin receptor blocker (ARB) therapy allowed (selection of which dictated by clinical care) if started three months or greater from first dose of IMP without change in dose. Aldosterone receptor antagonists (eg. Spironolactone or eplerenone) allowed if started 12 months or greater from first dose of Investigational Medicinal Product (IMP). No changes throughout the study allowed.
  4. Subjects aged 18 years and older, informed consent obtained directly. For subjects ages 7-17 years old (yo), both assent from the subject and permission from a parent or guardian.

You CAN'T join if...

  1. Clinically significant illness other than DMD
  2. Clinically significant laboratory abnormality not associated with DMD
  3. Major surgery within six weeks prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study procedures
  4. Require antiarrhythmic therapy and/or initiation of diuretic therapy for management of acute heart failure in the last 6 months
  5. A LVEF of < 35% by Cardiac Magnetic Resonance Imaging (CMR) and/or fractional shortening of < 15% based on echocardiography (ECHO) during screening
  6. A known bleeding disorder or has received anticoagulant treatment within 2 weeks of study entry
  7. Allergy to gadolinium contrast or known renal insufficiency defined as abnormal cystatin C or creatinine above the upper limit of normal for age. The male serum reference ranges as follows:
  8. Age 7-9 years - 0.2-0.6 mg/dL
  9. Age 10-11 years - 0.3-0.7 mg/dL
  10. Age 12-13 years - 0.4-0.8 mg/dL
  11. Age 14-15 years - 0.5-0.9 mg/dL
  12. Age 16 years or older - 0.8-1.3 mg/dL
  13. Non-MR compatible implants (e.g. neurostimulator, automatic implantable cardioverter-defibrillator [AICD])
  14. Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives (whichever is longer) of study entry
  15. . Any other condition that could interfere with the subject's participation

Locations

  • Mattel Children's Hospital accepting new patients
    Los Angeles California 90095 United States
  • Arkansas Children's Hospital accepting new patients
    Little Rock Arkansas 72202 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Cumberland Pharmaceuticals
ID
NCT03340675
Phase
Phase 2
Study Type
Interventional
Last Updated