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Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy (DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03340675
Recruitment Status : Recruiting
First Posted : November 13, 2017
Last Update Posted : August 2, 2022
Sponsor:
Collaborator:
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Cumberland Pharmaceuticals

Study Description
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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


Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Cardiomyopathy Cardiomyopathy, Dilated Drug: Ifetroban Drug: Placebo Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, placebo-controlled, double-blind, dose-ranging
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Each individual bottle is labelled with a unique numeric code that identifies the contents to the unblinded sponsor representative.
Primary Purpose: Treatment
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
Actual Study Start Date : October 19, 2020
Estimated Primary Completion Date : August 31, 2024
Estimated Study Completion Date : August 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Change from baseline in pulmonary function [ Time Frame: Baseline through 12 months ]
    Change from baseline in forced expiratory volume in 1 second

  7. 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.


Eligibility Criteria
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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03340675


Contacts
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Contact: Ines M Macias-Perez, PhD 6159795778 imaciasperez@cumberlandpharma.com
Contact: Ingrid Anderson, PhD, CCRP 615-255-0068 ext 250 ianderson@cumberlandpharma.com

Locations
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United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Annette Guy    501-364-3380    GuyEA@archildrens.org   
Principal Investigator: Markus Renno, MD         
United States, California
Mattel Children's Hospital Recruiting
Los Angeles, California, United States, 90095
Contact: Emilie Douine-Barthelemy    310-991-2674    EDouine@mednet.ucla.edu   
United States, District of Columbia
Children's National Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Robert Lowndes    301-512-3337    rlowndes@childrensnational.org   
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30341
Contact: Melissa Burnett    404-785-0381    melissa.burnett@choa.org   
United States, Illinois
Lurie Children's Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Kathleen Van't Hof       kvanthof@luriechildrens.org   
Principal Investigator: Katheryn Gambetta, MD         
United States, Indiana
Riley Children's Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Jennifer Howell    317-278-7818    jemrich@iu.edu   
United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Genila Bibat, MD       bibat@kennedykrieger.org   
Contact: Sharanya Suresh       suresh@kennedyKrieger.org   
Principal Investigator: Doris Leung, MD         
United States, Missouri
Saint. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jessie Schwieterman, PT, CCRP       j.schwieterman@wustl.edu   
Principal Investigator: Craig Zaidman, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Kenneth Mucheck       Kenneth.Mucheck@cchmc.org   
Contact: Remesha Palmer       Remesha.Palmer@cchmc.org   
Principal Investigator: Chet Villa, MD         
United States, Tennessee
Monroe Carrell Jr. Children's Hospital at Vanderbilt Recruiting
Nashville, Tennessee, United States, 37232
Contact: Kim Crum, RN, BS    615-936-2497    kimberly.crum@vumc.org   
Principal Investigator: Jonathan H Soslow, MD         
Sponsors and Collaborators
Cumberland Pharmaceuticals
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Larry Markham, MD Riley Children's Hospital
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03340675    
Other Study ID Numbers: CPI-IFE-007
FD-R-6371 ( Other Grant/Funding Number: FDA Orphan Products Development )
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
 Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Cardiomegaly
Laminopathies
Ifetroban
Platelet Aggregation Inhibitors