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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.
Neuromuscular Research Center of Arizona
Phoenix, Arizona, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
University of California, Davis Medical Center
Sacramento, California, United States
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
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.
Time frame: Baseline up to 100 weeks
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
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.
Time frame: Baseline up to 100 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
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.
Time frame: Baseline up to 100 weeks
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Stanford University Medical Center
Stanford, California, United States
University of Florida, Shands Hospital
Gainesville, Florida, United States
Rare Disease Research Center
Atlanta, Georgia, United States
Children's Hospital of Atlanta
Atlanta, Georgia, United States
University of Iowa Children's Hospital
Iowa City, Iowa, United States
St. Louis Children's Hospital
St Louis, Missouri, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
...and 3 more locations
Number of Participants With at Least One Abnormal Physical Examination Finding
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.
Time frame: Baseline up to 100 weeks
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
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.
Time frame: Baseline up to 96 weeks
Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
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.
Time frame: Baseline up to 96 weeks
Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at 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.
Time frame: Baseline, Week 48 and 96
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at 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.
Time frame: Baseline, Week 48 and 96