Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy (DMD)

March 5, 2024 updated by: Cumberland Pharmaceuticals

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:
        • Principal Investigator:
          • Markus Renno, MD
    • California
      • Los Angeles, California, United States, 90095
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
    • Georgia
      • Atlanta, Georgia, United States, 30341
        • Recruiting
        • Children's Healthcare of Atlanta
        • Contact:
    • Illinois
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Children's Hospital
        • Contact:
    • Maryland
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Saint. Louis Children's Hospital
        • Principal Investigator:
          • Craig Zaidman, MD
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Active, not recruiting
        • Monroe Carrell Jr. Children's Hospital at Vanderbilt

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  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, 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%.

  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.

Exclusion criteria:

  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:

    • 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
  8. Non-MR compatible implants (e.g. neurostimulator, automatic implantable cardioverter-defibrillator [AICD])
  9. Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives (whichever is longer) of study entry
  10. Any other condition that could interfere with the subject's participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Ifetroban - Low Dose
Weight based, once daily oral ifetroban
Drug: Ifetroban
Weight based, once daily oral ifetroban
Experimental: Oral Ifetroban - High Dose
Weight based, once daily oral ifetroban
Drug: Ifetroban
Weight based, once daily oral ifetroban
Placebo Comparator: Placebos
Matching Placebo
Drug: Placebo
Matching oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events (safety & tolerability)
Time Frame: Baseline through 12 months
Percentage of subjects with one or more treatment emergent adverse event
Baseline through 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics Area under the curve
Time Frame: Day 0 and Day 7
Measurements of Area under the curve concentration of ifetroban and its acyl glucuronide metabolite
Day 0 and Day 7
Pharmacokinetics maximum serum concentration (Cmax)
Time Frame: Day 0 and Day 7
Measurements of maximum serum concentration (Cmax) of ifetroban and its acyl glucuronide metabolite
Day 0 and Day 7
Pharmacokinetics time to reach Cmax (Tmax) concentration
Time Frame: Day 0 and Day 7
Measurement of time to reach Cmax (Tmax) concentration of ifetroban and its acyl glucuronide metabolite
Day 0 and Day 7
Pharmacokinetics plasma terminal half-life concentration
Time Frame: Day 0 and Day 7
Measurement of plasma terminal half-life concentration of ifetroban and its acyl glucuronide metabolite
Day 0 and Day 7
Change from baseline in left ventricular ejection fraction
Time Frame: Baseline through 12 months
There should be no change in left ventricular ejection fraction. Patients with DMD have a decline.
Baseline through 12 months
Change from baseline in pulmonary function
Time Frame: Baseline through 12 months
Change from baseline in forced expiratory volume in 1 second
Baseline through 12 months
Change from baseline in quality-of-life
Time Frame: 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.
Baseline through 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cumberland Pharmaceuticals

Collaborators

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Larry Markham, MD, Riley Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2020

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

November 3, 2017

First Submitted That Met QC Criteria

November 8, 2017

First Posted (Actual)

November 13, 2017

Study Record Updates

Last Update Posted (Actual)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPI-IFE-007
  • FD-R-6371 (Other Grant/Funding Number: FDA Orphan Products Development)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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