Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

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

Population: Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

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

Population: Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at 1 assessment post-enrollment assessment.

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

Population: Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment postenrollment assessment.

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

Population: Full set included all participants who were enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

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

Population: Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

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

Population: Full set included all participants who were enrolled in the eteplirsen group and received at least 1 dose of eteplirsen as well as all participants who were enrolled in the untreated group and had at least 1 assessment post-enrollment assessment.

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

Population: Muscle Biopsy Set included all participants who received at least 1 dose of eteplirsen and who had data from both baseline (pre-treatment) and Week 48 or 96 (on-treatment) muscle biopsy samples. Data for this outcome was not planned to be collected and analyzed for control group (untreated) (non-exon 51 amenable participants). Here, number of participants analyzed signifies participants who were evaluable at specific time point.

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

Population: Muscle Biopsy Set included all participants who received at least 1 dose of eteplirsen and who had data from both baseline (pre-treatment) and Week 48 or 96 (on-treatment) muscle biopsy samples. Data for this outcome was not planned to be collected and analyzed for control group (untreated) (non-exon 51 amenable participants). Here, number of participants analyzed signifies participants who were evaluable at specific time point.