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Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02420379
Recruitment Status : Completed
First Posted : April 17, 2015
Results First Posted : July 22, 2020
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Brief Summary:
This is an open-label study to assess the safety, tolerability, efficacy and pharmacokinetics of eteplirsen in patients with early stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy (DMD) Drug: eteplirsen Phase 2

Detailed Description:

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy.

Population and serial PK will be collected.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy
Actual Study Start Date : June 30, 2015
Actual Primary Completion Date : December 17, 2018
Actual Study Completion Date : December 17, 2018


Arm Intervention/treatment
Experimental: Open-Label
Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .
Drug: eteplirsen
Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.
Other Names:
  • AVI-4658
  • EXONDYS 51®

No Intervention: Control Group
Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.



Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation [ Time Frame: Baseline up to 100 weeks ]
    Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug [up to 100 weeks]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  2. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs [ Time Frame: Baseline up to 100 weeks ]
    Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

  3. Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs [ Time Frame: Baseline up to 100 weeks ]
    Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

  4. Number of Participants With at Least One Abnormal Physical Examination Finding [ Time Frame: Baseline up to 100 weeks ]
    Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.

  5. Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs [ Time Frame: Baseline up to 96 weeks ]
    Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.

  6. Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs [ Time Frame: Baseline up to 96 weeks ]
    Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.


Secondary Outcome Measures :
  1. Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96 [ Time Frame: Baseline, Week 48 and 96 ]
    Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.

  2. Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96 [ Time Frame: Baseline, Week 48 and 96 ]
    Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 6 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male 4-6 years of age.
  • Diagnosis of DMD, genotypically confirmed.
  • Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.
  • Intact right and left biceps muscles or two alternative upper arm muscle groups.
  • Parent that is willing to provide consent and comply with study procedures.

Exclusion Criteria:

  • Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
  • Previous or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.
  • Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.
  • Presence of other clinically significant illness.

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): NCT02420379


Locations
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United States, Arizona
Neuromuscular Research Center of Arizona
Phoenix, Arizona, United States, 85028
United States, California
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
University of California, Davis Medical Center
Sacramento, California, United States, 95817
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
University of Florida, Shands Hospital
Gainesville, Florida, United States, 32610
United States, Georgia
Rare Disease Research Center
Atlanta, Georgia, United States, 30318
Children's Hospital of Atlanta
Atlanta, Georgia, United States, 30324
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Shriners Hospital for Children
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
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Study Director: Medical Director Sarepta Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Sarepta Therapeutics, Inc.:
Statistical Analysis Plan  [PDF] February 11, 2019
Study Protocol  [PDF] June 8, 2017

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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02420379    
Other Study ID Numbers: 4658-203
First Posted: April 17, 2015    Key Record Dates
Results First Posted: July 22, 2020
Last Update Posted: January 25, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sarepta Therapeutics, Inc.:
DMD
Duchenne muscular dystrophy
eteplirsen
Dystrophin
exon 51
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked