Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy

NCT03340675 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CPI-IFE-007FD-R-6371
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 10

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

Conditions

Duchenne Muscular Dystrophy Cardiomyopathy; Cardiomyopathy, Dilated

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Percentage of subjects with one or more treatment emergent adverse event

  Baseline through 12 months

Secondary Outcomes (14)

• Pharmacokinetics Area Under the Curve

  Pre-dose and at 0.5, 1.0, 4.0, 8.0 and 24.0 h post-dose on Day 0 and pre-dose and 0.5 h post-dose on Day 7

• Pharmacokinetics Maximum Serum Concentration (Cmax)

  Pre-dose and at 0.5, 1.0, 4.0, 8.0 and 24.0 h post dose on Day 0 and pre-dose and 0.5 h post-dose on Day 7

• Pharmacokinetics Time to Reach Cmax (Tmax) Concentration

  Pre-dose and at 0.5, 1.0, 4.0, 8.0 and 24.0 h post dose on Day 0 and pre-dose and 0.5 h post-dose on Day 7

• Pharmacokinetics Plasma Terminal Half-life Concentration

  Pre-dose and at 0.5, 1.0, 4.0, 8.0 and 24.0 h post dose on Day 0 and pre-dose and 0.5 h post-dose on Day 7

• Change From Baseline in Left Ventricular Ejection Fraction

  Baseline visit and Month 12 visit

Study Arms (3)

Oral Ifetroban - Low Dose

EXPERIMENTAL

Weight based, once daily oral ifetroban

Drug: Ifetroban

Oral Ifetroban - High Dose

EXPERIMENTAL

Weight based, once daily oral ifetroban

Drug: Ifetroban

Placebos

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

Ifetroban DRUG

Weight based, once daily oral ifetroban

Oral Ifetroban - High Dose; Oral Ifetroban - Low Dose

Placebo DRUG

Matching oral placebo

Placebos

Eligibility Criteria

• Age: 7 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Stable dose of oral corticosteroids for at least 8 weeks or has not received corticosteroids for at least 30 days.
• 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, except in the event of a decline in left ventricular ejection fraction (LVEF) \>5% following the baseline CMR as measured by a subsequent CMR at the same center. Should this occur, changes in cardiac medications are allowed on the study.
• a. Late-stage cohort: Subjects are eligible for the late-stage cohort if the subject has: i. LVEF 35%-45% by cine cardiac magnetic resonance imaging (MRI) or echocardiography or ii. historically documented LVEF 35%-45% by cine cardiac magnetic resonance imaging (MRI) or echocardiography and if their baseline MRI is less than 50%.
• 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 may not qualify if:

• Clinically significant illness other than DMD
• Clinically significant laboratory abnormality not associated with DMD
• 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
• Require antiarrhythmic therapy and/or initiation of diuretic therapy for management of acute heart failure in the last 6 months
• A LVEF of \< 35% by Cardiac Magnetic Resonance Imaging (CMR) and/or fractional shortening of \< 15% based on echocardiography (ECHO) during screening
• A known bleeding disorder or has received anticoagulant treatment within 2 weeks of study entry
• 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:
• Age 7-9 years - 0.2-0.6 mg/dL
• Age 10-11 years - 0.3-0.7 mg/dL
• Age 12-13 years - 0.4-0.8 mg/dL
• Age 14-15 years - 0.5-0.9 mg/dL
• Age 16 years or older - 0.8-1.3 mg/dL
• Non-MR compatible implants (e.g. neurostimulator, automatic implantable cardioverter-defibrillator \[AICD\])
• Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives (whichever is longer) of study entry
• Any other condition that could interfere with the subject's participation

Sponsors & Collaborators

• Cumberland Pharmaceuticals: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (10)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Mattel Children's Hospital

Los Angeles, California, 90095, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30341, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Saint. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Monroe Carrell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Mitchell R, Frederick NE, Holzman ER, Agobe F, Allaway HCM, Bagher P. Ifetroban reduces coronary artery dysfunction in a mouse model of Duchenne muscular dystrophy. Am J Physiol Heart Circ Physiol. 2021 Jul 1;321(1):H52-H58. doi: 10.1152/ajpheart.00180.2021. Epub 2021 May 28.

  PMID: 34048282 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Dilated

Interventions

ifetroban

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Ines Macias-Perez
• Organization: Cumberland Pharmaceuticals

imaciasperez@cumberlandpharma.com

(615) 564-2188

Study Officials

• Larry Markham, MD

  Riley Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each individual bottle is labelled with a unique numeric code that identifies the contents to the unblinded sponsor representative.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blind, dose-ranging

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 13, 2017
• Study Start: October 19, 2020
• Primary Completion: March 6, 2024
• Study Completion: January 23, 2026
• Last Updated: March 17, 2026
• Results First Posted: January 26, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)