A 96-week, double-blind, placebo-controlled followed by a 48 week open label extension research study to evaluate the effectiveness and safety of investigational products, SRP-4045 and SRP-4053, in patients with Duchenne muscular dystrophy.
For US Patients and Audiences Only
Exon Skipping for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare, life-shortening genetic disorder that affects boys and causes their muscles to break down and lose strength over time. DMD is caused by specific errors (mutations) in the gene that codes for dystrophin. Dystrophin is a protein that plays a key role in the function of muscle cells and protects them from damage as muscles contract and relax. These mutations in the dystrophin gene lead to a lack of dystrophin protein in muscles. Without enough dystrophin, muscles gradually grow weaker until they can’t move at all, and eventually breathing and heart function are lost. Sarepta's investigational therapies, SRP-4045 and SRP-4053, are being evaluated in the ESSENCE study as an approach to help muscles make a shorter form of dystrophin protein and possibly slow the progression of DMD.
Duchenne is caused by mutations to the dystrophin gene. Most commonly, one or more exons (a portion of the gene) are missing, and the remaining exons don’t ﬁt together properly. Because of this error, cells cannot make dystrophin, a protein muscles need to work properly. Without dystrophin, muscle cells are damaged, and, over time, are replaced with scar tissue and fat.
Our investigational therapies in the ESSENCE study use a technique referred to as exon skipping. Skipping a specific exon next to the mutation is intended to allow the body to make a shortened form of the dystrophin protein.
Purpose of the ESSENCE Study
The purpose of this Phase III research study is to evaluate the safety and effectiveness of SRP-4045 and SRP-4053 in boys with DMD, who have a deletion that is potentially responsive to, or amenable to exon 45 or exon 53 skipping. ESSENCE is a randomized, placebo-controlled study. Each study participant will be randomly assigned to receive either active study drug (SRP-4045 or SRP-4053, depending on his deletion type) or placebo. Placebo is made to look just like the active study drug, but it will not contain any active substance. Researchers use a placebo to see if the active study drug works and to see how safe and effective it is compared to not taking anything. This trial design is the best way to get a clear answer about the safety and effectiveness of a new drug, and is usually required by regulatory authorities in the approval process for a drug.
DMD patients with deletions potentially responsive to, or amenable to exon-45 skipping
DMD patients with deletions potentially responsive to, or amenable to exon-53 skipping
DMD patients potentially amenable to either exon 45 or exon 53 skipping in this trial are randomly assigned to receive inactive placebo during the study Two out of every three patients will receive the active study drug.
Why Consider Enrolling in This Trial?
Patients who complete the placebo-controlled part of the study will be eligible to participate in the 1-year open-label extension period. After this they will also be eligible for a long term open-label extension period. Open-label means all patients will receive the active study drug and you and the study team will know that your son is receiving it.
Who is Eligible?
Boys with DMD who are 7 – 13 years old and can walk between 300 and 450 meters on the 6-minute walk test.
Have a genetic test that shows a mutation in the dystrophin gene that may be treated by skipping exon 45 or 53*. Talk to your doctor if you are unsure.
Have been on a stable dose of corticosteroids (such as prednisone or deﬂazacort) for at least 6 months.
Have stable lung (breathing) and heart function.
There are additional requirements for participation and those will be reviewed with patients and their families during the screening process.
Deletions potentially amenable to exon 45 skipping include but are not limited to 12–44, 18–44, 44, 46–47, 46–48, 46–49, 46–53, or 46–55. Deletions amenable to exon 53 skipping include but are not limited to 42-52, 45-52, 47-52, 48-52, 49-52, 50-52, 52, and 54-58.
What is a randomized placebo-controlled trial?In a randomized, placebo-controlled study, each participant is picked randomly, by chance (like tossing a coin) to receive either active study drug, or placebo. Placebo is made to look just like the active study drug, but it does not contain any active substance.
What is the chance that my son will receive placebo vs. active study drug?If your son takes part in this study, he will have a 2 in 3 chance of receiving active study drug and a 1 in 3 chance of receiving placebo during the double-blind, placebo-controlled part of the study (up to 96 weeks).
If my son gets the placebo drug, will he receive active drug at any point in the study?Patients who complete the placebo-controlled part of the study will be eligible to participate in the 1-year open-label extension period. After this they will also be eligible for a long term open-label extension study. Open-label means all patients will receive active study drug and you and the study team will know that your son is receiving it.
How many boys will be enrolled in this study and where is it being run?Approximately 222 boys are planned to be enrolled in this study. The trial is being run globally, check locations for a site near you.
Why is Sarepta sponsoring a randomized placebo-controlled trial?Researchers use a placebo to see if the active study drug works and to see how safe. A placebo-controlled trial design is the best way to get a clear answer about the safety and effectiveness of a new drug and is usually required by regulatory authorities in the approval process for a drug.
Why is the placebo-controlled period of this study 96 weeks?Based on Sarepta’s clinical trials and analyses, this may be the earliest time to potentially see a treatment effect on the six-minute walk test (6MWT).
Why is the baseline six minute walk test (6MWT) between 300 - 450 meters?Boys in this range of the six minute walk distance are at the stage of their DMD when they are most likely to show an effect of treatment.
Why is the age range 7 - 13 years old?To learn if SRP-4045 and SRP-4053 are effective in slowing the progression of DMD, this study will compare 6MWT results between patients who receive active study drug and patients who receive placebo. To allow the clearest comparison, all boys in the study need to be at a similar stage of their DMD.
Will I be paid for participating?Generally, reasonable costs associated with participation in the study will be prepaid or reimbursed by Sarepta in accordance with the approved travel policy for the study procedures performed as part of the study. Information will be provided by the study site.
Why do you need to collect biopsies?This study will measure the change in the amount of dystrophin protein in muscle after 48 weeks of treatment in some muscle biopsy samples and after 96 weeks of treatment in others. Because SRP-4045 and SRP-4053 are designed to increase levels of dystrophin in muscle, the only way to show that exon skipping by SRP-4045 or SRP-4053 is working as intended is to test muscle directly. This cannot be studied by testing blood or urine, for example.
How long is this clinical trial?Your son’s participation in this clinical trial could be up to 3 years long. There is a 96-week double-blind placebo-controlled period during which 2/3 of the participants receive active study drug and 1/3 of the patients receive placebo. The placebo-controlled period is followed by an up to 48-week open label period in which all patients receive active study drug.
What are some of the activities my son will be required to do to take part in this study?
- This clinical trial includes weekly visits to your nearest clinical trial site, where your son will receive an infusion of active study drug or placebo (depending on which treatment group your son is assigned to, and what part of the study he’s in). Your son will also periodically have blood drawn and physical exams done at your local site.
- Approximately every 12 weeks there will be functional assessments which include tests of walking distance, other walking-related activities, muscle strength, breathing and heart function. You may need to travel to another site other than your nearest clinical trial site to do these functional assessments.
- There are also 2 muscle biopsies, 1 at the beginning of the study and 1, after either approximately one or two years. Depending on where you live it may be necessary to travel for the biopsy surgery.
- You can learn more about all of the requirements and activities in this clinical trial from the study doctor.
What risks are associated with this study?As with all clinical studies, there can be risks associated with possible side effects of taking the study drug and with the standard medical tests carried out as part of the study at each visit. Information on the possible side effects you may experience in the study is available in the consent form and should be discussed with your study doctor.
What are some benefits to being a part of this clinical trial?The potential benefits of SRP-4045 and SRP-4053 in patients with DMD are unknown. Even if you do not benefit from being in this study, we might learn something that could advance research and help others.