Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy
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|ClinicalTrials.gov Identifier: NCT02420379|
Recruitment Status : Completed
First Posted : April 17, 2015
Results First Posted : July 22, 2020
Last Update Posted : January 25, 2021
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy (DMD)||Drug: eteplirsen||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .
Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.
No Intervention: Control Group
Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02420379
|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|
|Study Director:||Medical Director||Sarepta Therapeutics, Inc.|