COMMITTED TO STRENGTHENING TREATMENT OPTIONS FOR BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Our mission is to help build a body of research for future generations of boys with Duchenne Muscular Dystrophy. The MIS51ON clinical research study is researching the investigational use of a medication designed to target Duchenne gene mutations amenable to exon 51 skipping. This study is seeking to determine if a higher dose of the study drug, also known as etiplirsen, is also safe and/or effective in treating Duchenne.
COMMITTED TO STRENGTHENING TREATMENT OPTIONS FOR BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Our mission is to help build a body of research for future generations of boys with Duchenne Muscular Dystrophy. The MIS51ON clinical research study is researching the investigational use of a medication designed to target Duchenne gene mutations amenable to exon 51 skipping. This study is seeking to determine if a higher dose of the study drug, also known as etiplirsen, is also safe and/or effective in treating Duchenne.
Exon Skipping in Duchenne Muscular Dystrophy
The Genetics of Duchenne
Duchenne is a rare, life-shortening genetic disorder that affects boys and causes their muscles to break down and lose strength over time. Duchenne 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.
What do I need to know about Exon Skipping?
Commonly with Duchenne, one or more exons (parts of the gene) are missing, causing errors in the instructions for making dystrophin. This results in the body not being able to produce enough, or any, working dystrophin protein. The goal of exon skipping is to allow the body to make a shorter form of the dystrophin protein, which may help to improve muscle function.
The dystrophin gene is made up of exons that are linked together to provide instructions for making dystrophin. With 79 exons, the dystrophin gene is the largest in the body. Think of the exons on the dystrophin gene as a chain of puzzle pieces, each with a special connection that allows one piece to connect to another. To complete the chain, the connections between certain pieces must match.
In this image, you can see that exon 50 is missing. The result is that exons 49 and 51 are not able to connect because their connectors are different shapes and don’t fit together. In the dystrophin gene, this missing exon would prevent the body from being able to read the instructions for making the dystrophin protein.
By moving certain exons aside, we can potentially “skip over” them to find an exon with the right connector. The new chain would be shorter, but the pieces will be connected (and therefore able to better produce dystrophin). Just as we skipped over one of the pieces, the study drug is designed to skip over exon 51.
The result of this exon 51 skipping may help increase production of this shorter form of dystrophin and improve muscle function.
What Do I Need to Know About the Study Drug?
Who is Eligible to participate?
- Male, 4 to 13 years of age (inclusive)
- Have been diagnosed with Duchenne with a gene mutation amenable to exon 51 skipping
- Have never received any gene therapy or gene editing treatment. If previously received any other type of treatment for Duchenne, please discuss the specific treatment(s) with the study doctor.
- Have been on a stable dose of oral corticosteroids for at least 12 weeks
- Ambulatory, able to walk independently without assistive devices
Additional requirements for participation may apply and will be discussed with the study doctor during the Screening Visit. For a full list of eligibility criteria, please visit ClinicalTrials.gov.
Who is Eligible to participate?
Individuals may be eligible to participate in MIS51ON if they meet the following eligibility criteria:
- Male, 4 to 13 years of age (inclusive)
- Have been diagnosed with Duchenne with a gene mutation amenable to exon 51 skipping
- Have never received any gene therapy or gene editing treatment. If previously received any other type of treatment for Duchenne, please discuss the specific treatment(s) with the study doctor.
- Have been on a stable dose of oral corticosteroids for at least 12 weeks
- Ambulatory, able to walk independently without assistive devices
Additional requirements for participation may apply and will be discussed with the study doctor during the Screening Visit. For a full list of eligibility criteria, please visit ClinicalTrials.gov.
What to Know About Sarepta MIS51ON
Individuals interested in participating in the MIS51ON study will attend screening visits with a study doctor at a participating center. During the screening visits, the study doctor will assess eligibility for the study.
They will ask questions about the child’s health and complete several clinical tests including a physical exam, blood and urine collection, functional movement assessments, and heart monitoring to determine if they qualify as a participant in the MIS51ON study.
If an individual qualifies for participation in MIS51ON, they will be randomly assigned to the study drug at either the higher dose or 30mg/kg dose.
Study Participation
SareptAlly is a clinical trial patient matching service for Sarepta-sponsored studies.
A Patient Navigator can help you understand your clinical trial options.
Frequently Asked Questions
Will all individuals enrolled in this study receive treatment with the study drug?
Yes, all patients enrolled in this study will receive the study drug. There is no placebo group for this study.
Are individuals who are currently or have previously been treated with the study drug eligible for this study?
Individuals who are currently or have previously been treated with the study drug may be eligible for this study with no washout period.
How many males will be enrolled in this study and where is it being run?
Up to 154 patients are planned to be enrolled in this study globally. 144 of these patients will be enrolled in the double-blind dose-finding and comparison part of the study.
For a full list of study locations please go to clinicaltrials.gov and search “NCT03992430”.
Who determines eligibility to participate?
The study doctor determines whether a patient meets all the inclusion criteria (things that must be met to be eligible) and none of the exclusion criteria (things that must not be met to be eligible) for the study. The study doctor determines eligibility by performing evaluations and tests which give them information on if the patient meets the criteria.
Are biopsies collected in this study?
Yes, a total of 2 biopsies are collected in the Dose-Finding and Dose Comparison (Part 2) part of the study. All Part 2 patients will undergo a muscle biopsy before taking any dose of the study drug. The patient will undergo one more biopsy at either week 24, week 48, or week 144 (depending on which dose group they were assigned to).
Why are biopsies being collected?
This study will measure the change in the amount of dystrophin protein in muscle after 24, 48, and/or 144 weeks of treatment. This will be a component in determining a single high dose of the study drug.
The way to show that exon skipping induced by the study drug, which is designed to increase levels of dystrophin in muscle, is working as intended is to test muscle directly. This cannot be done by testing blood or urine, for example.
Is there a Cost to Participate?
If your child chooses to and is eligible to participate, you will not receive any payment, either directly or indirectly, for his participation. Sarepta Therapeutics will pay for the clinical research study costs. In addition, reasonable travel-related expenses (e.g., mileage, parking, overnight stays) may be covered for you in accordance with the travel policy for the clinical research study. Please speak with the study doctor and staff for more information.
What risks are associated with this study?
As with any clinical research study, there are potential risks and benefits to participating in the MIS51ON clinical research study. Your child’s health may improve, get worse, or not change at all. In addition, there are potential risks to taking the study drug and undergoing some of the study-related procedures.
Your child’s health and safety are always the top priority of the study team. If the study doctor believes that study participation is no longer appropriate or may be placing your child at unnecessary risk, he or she will consult with you to discuss other potential options to consider.
To understand what these risks are, please carefully read the informed Consent Form and speak with the study doctor.
Is study participation voluntary?
Participating in the MIS51ON clinical research study is completely voluntary. Your child may choose to stop participating at any time and for any reason.
What are some benefits of being a part of this clinical research study?
While no benefit can be guaranteed from participation in the MIS51ON study, some benefits may include:
- Contribute to what is currently known about the progression of Duchenne
- Help others by contributing to medical research that may trigger the development of Duchenne therapies.
Still have questions?
If you have further questions about the trial or participation, you may:
Trial Locations
For a full list of participating study centers, please visit clinicaltrials.gov and search “NCT03992430”.
Sarepta is committed to patients and families living with DMD.
