DYNEDMD: Study to Measure the Safety and Effectiveness of DYNE-251 in Boys with Duchenne Muscular Dystrophy

This first-in-human study evaluates the safety and effectiveness of multiple ascending doses of DYNE-251 administered intravenously to participants with DMD caused by mutations amenable to exon 51 skipping. These data will also identify the therapeutic dose of DYNE-251, which may be used in future studies.

DYNE-251 is an exon-skipping oligonucleotide that’s designed to specifically target muscle and cardiac tissue, intended to increase dystrophin production in these selected tissues.

Seven ascending sequential dose cohorts and a fifth optional cohort are planned. Each participant will undergo an up-to-45-day pretreatment screening period, a 24-week placebo-controlled period, a 24-week open-label period, and a 96-week long-term extension. Participants will be admitted to the hospital after their first infusion, then have monthly outpatient infusions for the remainder of the study.

Primary Objectives

• To test the safety of DYNE-251 in young males with DMD
• To test if and how well DYNE-251 works in treating young males with DMD
• To test the pharmacokinetics of DYNE-251 by measuring the levels of DYNE‑251 in blood and in muscle tissue
• To test the pharmacodynamics of DYNE-251
• To determine whether there are biomarkers that help to understand how DYNE-251 might treat DMD
• To identify the dose of DYNE-251 that provides the most benefit to patients with acceptable safety

Eligibility criteria

Inclusion criteria include:

• Males aged 4 to 16
• Diagnosed with DMD with a deletion that is amenable to exon 51 skipping
• Currently receiving a stable dose of steroids
• Have stable heart activity with left ventricular ejection fraction greater than 50%

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee 
Collaborating sites in the U.S.

About this study

This study tests a new drug called DYNE-251 in young males with Duchenne muscular dystrophy to see if it can improve muscle strength, function, and quality of life. The drug works by increasing the production of dystrophin in the muscles. This drug may work for those who have DMD and have a specific genetic change. This change means an area of DNA on the dystrophin gene, called exon 51, is missing. DYNE-251 is an experimental drug that has not been approved to treat DMD in people. This study is the first time DYNE-251 is being tested in humans.

Study participants will be randomly assigned to receive either the study drug or a placebo for six months. The drug will be given through the vein. This process is called infusion. They will receive the study drug for up to 2.5 years. After the first infusion of the study drug, participants will stay at the hospital to be monitored. Then they will have infusions every four weeks. They can go home after each of these infusions and do not need to stay in the hospital for monitoring.

Purpose of this clinical trial

The main goal of this study is to see if DYNE-251 is safe to use in young males with DMD. Researchers also want to find out how well DYNE-251 treats the disease and how it affects the body in other ways.

Eligibility overview

• Males aged 4 to 16 with a diagnosis of Duchenne muscular dystrophy