Part 1 (dose escalation) will evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10 participants with DMD; Part 2 (dose finding and dose comparison) will evaluate the efficacy and safety of the high doses (100 mg/kg and 200 mg/kg) of eteplirsen compared with that of the 30 mg/kg dose of eteplirsen, in approximately 144 participants with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.

Inclusion Criteria:

• Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.
• Ambulatory participant, able to perform TTRISE in 10 seconds or less at the time of screening visit.
• Able to walk independently without assistive devices.
• Have intact right and left biceps muscles or an alternative upper arm muscle group.
• Have been on a stable dose or dose equivalent of oral corticosteroids for at least 12 weeks prior to randomization and the dose is expected to remain constant (except for modifications to accommodate changes in weight and stress-related needs as per the recently published guidelines throughout the study.
• For ages 7 years and older, has stable pulmonary function (forced vital capacity ≥50 percent (%) of predicted and no requirement for nocturnal ventilation). For ages 4 to 6 years, does not require support from ventilator or non-invasive ventilation at time of screening.

Exclusion Criteria:

• Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
• Current or previous treatment with any other experimental pharmacologic treatment for DMD or any prior exposure to antisense oligonucleotide, gene therapy or gene editing; except the following: Ezutromid in the last 12 weeks prior to first dose; Drisapersen in the last 36 weeks prior to first dose; Suvodirsen in the last 12 weeks prior to first dose; Vamorolone in the last 12 weeks prior to first dose; Eteplirsen (previous or current use); and Tamoxifen in the last 4 weeks prior to first dose.
• Major surgery within 3 months prior to randomization.
• Presence of any other significant neuromuscular or genetic disease other than DMD.
• Presence of any known impairment of renal function and/or other clinically significant illness.
• Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than <50% on the screening echocardiogram or Fridericia's correction formula (QTcF) ≥450 millisecond based on the screening electrocardiograms (ECGs).

Other inclusion/exclusion criteria apply.

Part 1 is open-label, dose escalation; Part 2 is double-blind, dose finding, and dose comparison