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.

The Problem

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.

Missing Exon

Exon Skipping

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.

SRP–4045

DMD patients with deletions potentially responsive to, or amenable to exon-45 skipping

SRP–4053

DMD patients with deletions potentially responsive to, or amenable to exon-53 skipping

Placebo

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 2-year 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.

When 75% of patients have been in the trial for 48 weeks a group of independent experts will review key study results to decide if the information already gathered is enough to prove that SRP-4045 and SRP-4053 are safe and effective. If so, patients will have the opportunity to roll into the open-label period of the study early and receive active study drug. If the experts decide that more information is still needed, then the placebo-controlled period will continue out to Week 96 as originally planned.

This means that the faster patients enroll in the trial, the sooner experts will have enough results to review. This also means that patients on placebo may be able to transfer from placebo to active study drug.

 

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.

Frequently Asked Questions

Q:

What is a randomized placebo-controlled trial?

A:

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.

Q:

What is the chance that my son will receive placebo vs. active study drug?

A:

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).

Q:

If my son gets the placebo drug, will he receive active drug at any point in the study?

A:

Patients who complete the placebo-controlled part of the study will be eligible to participate in the 2-year open-label extension period. Open-label means all patients will receive active study drug and you and the study team will know that your son is receiving it.

Q:

Why is Sarepta sponsoring a randomized placebo-controlled trial?

A:

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.

Q:

How many boys will be enrolled in this study and where is it being run?

A:

Approximately 99 boys are planned to be enrolled in this study. We plan to have clinical trial sites in United States.

Q:

Why is the placebo-controlled period of this study 96 weeks?

A:

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).

Q:

Why is the baseline six minute walk test (6MWT) between 300 - 450 meters?

A:

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.

Q:

Why is the age range 7 - 13 years old?

A:

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.

Age 7-13 is the age range when boys with DMD start to have a decrease in how far and how fast they can walk. In addition, all patients need to be on steroids to enter the study. Steroids are usually not begun until 4-8 years of age. For these reasons, it is easiest to see an effect of treatment on walking ability in boys who are 7 to 13 years of age.

Q:

Will I be paid for participating?

A:

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.

Q:

Why do you need to collect biopsies?

A:

This study will measure the change in the amount of dystrophin protein in muscle after 48 weeks of treatment. 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.

Q:

How long is this clinical trial?

A:

Your son’s participation in this clinical trial could be up to 4 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 96-week open label period in which all patients receive active study drug.

Q:

What are some of the activities my son will be required to do to take part in this study?

A:
  • 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 approximately one year. 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.
Q:

What risks are associated with this study?

A:

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.

Q:

What are some benefits to being a part of this clinical trial?

A:

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.

Find a Trial Location

Type in your location to find the nearest clinical trial site. Additional information can be found here.

If interested in this study, please contact a clinical trial site or your healthcare provider.

View List of Locations

All Trial Locations

    United States

    • Arizona
      Neuromuscular Research Center
      4545 E Shea Blvd
      Phoenix, AZ 85028
      Contact: Kristy Osgood
      480-314-1007
      kosgood@nrcaz.com

      Principal Investigator: Kumaraswamy Sivakumar, MD
      Status: recruiting
    • California
      Children’s Hospital Los Angeles
      4650 W Sunset Blvd
      Los Angeles, CA 90027
      Contact: Claudia Dozal
      323-361-5825
      cdozal@chla.usc.edu

      Principal Investigator: Leigh Maria Ramos-Platt, MD
      Status: recruiting
    • California
      David Geffen School of Medicine, UCLA
      10833 Le Conte Ave
      Los Angeles, CA 90095
      Contact: Michael Bonitati
      310-825-3264
      MBonitati@mednet.ucla.edu

      Principal Investigator: Perry Shieh, MD, PhD
      Status: recruiting
    • California
      Stanford University School of Medicine/Medical Center
      291 Campus Drive
      Stanford, CA 94305
      Contact: Carolyn Mclaughlin
      650-206-3178
      cjmclaug@stanford.edu

      Principal Investigator: John Day, MD
      Status: recruiting
    • California
      Rady Children’s Hospital San Diego/ UCSD
      3020 Children's Way
      San Diego, CA 92123
      Contact: Contact: Rosabel Agbayani
      858-966-8208
      ragbayani@rchsd.org

      Principal Investigator: Carla Grosmann, MD
      Status: recruiting
    • Connecticut
      Connecticut Children’s Medical Center
      282 Washington Street
      Hartford, CT 06106
      Contact: Contact: Hendriana Nielsen
      (860) 837-5881
      hnielsen@connecticutchildrens.org

      Principal Investigator: Gyula Acsadi, MD, PhD
      Status: recruiting
    • Florida
      NW Florida Clinical Research Group, LLC
      400 Gulf Breeze Pkwy
      Gulf Breeze, FL 32561
      Contact: Shae Lancelin shae.lancelin@cneurology.com
      Principal Investigator: Ben Renfroe, MD
      Status: recruiting
    • Florida
      University of Florida
      2004 Mowry Road
      Gainesville, FL 32610
      Contact: Norane Shehab
      (352) 294-8705
      norane.shehab@ufl.edu


      Principal Investigator: Barry Byrne, MD, PhD
      Status: recruiting
    • Georgia
      Center for Integrative Rare Disease Research (CIRDR)
      1891 Howell Mill Road, NW
      Atlanta, GA 30318
      Contact: Contact: Krystal Reese
      404-829-2380
      kreese@rarediseaseresearch.com

      Principal Investigator: Han Phan, MD
      Status: recruiting
    • Iowa
      University of Iowa Children’s Hospital
      200 Hawkins Dr
      Iowa City, IA 52242
      Contact: Carrie Stephan
      319-356-2673
      carrie-stephan@uiowa.edu

      Principal Investigator: Katherine Mathews, MD
      Status: recruiting
    • Illinois
      Ann and Robert H. Lurie Children’s Hospital of Chicago
      225 E Chicago Ave
      Chicago, IL 60611
      Contact: Theresa Oswald
      312-227-4483
      TOswald@luriechildrens.org

      Principal Investigator: Nancy Kuntz, MD
      Status: recruiting
    • Kansas
      University of Kansas, Medical Center
      3901 Rainbow Boulevard
      Kansas City, KS 66160
      Contact: Kiley Sims
      ksims2@kumc.edu

      Principal Investigator: Jeffery Statland, MD
      Status: recruiting
    • Massachusetts
      Boston Children’s Hospital
      300 Longwood Avenue
      Boston, MA 02115
      Contact: Timothy Harrington
      857-218-4677
      timothy.harrington@childrens.harvard.edu

      Principal Investigator: Basil Darras, MD
      Status: recruiting
    • Missouri
      St. Louis Children’s Hospital
      400 S Kingshighway Blvd
      St. Louis, MO 63110
      Contact: Traci Christenson
      314-362-6991
      christensont@wustl.edu

      Principal Investigator: Ann M Connolly, MD
      Status: recruiting
    • Nevada
      Las Vegas Clinic
      351 N Buffalo Dr
      Las Vegas, NV 89145
      Contact: Kaitlyn McKenna
      702-505-4230
      mckenna.k@lasvegasclinic.org

      Principal Investigator: Jonathan McKinnon, MD
      Status: recruiting
    • New York
      University of Rochester Clinical Research Center
      500 Joseph C Wilson Blvd
      Rochester, NY 14627
      Contact: Patricia Smith
      585-275-4339
      Patty_Smith@URMC.Rochester.edu

      Principal Investigator: Emma Ciafaloni, MD
      Status: recruiting
    • Ohio
      Cincinnati Children’s Hospital Medical Center
      3333 Burnet Ave
      Cincinnati, OH 45229
      Contact:
      Principal Investigator: John Jefferies, MD
      Status: non-recruiting
    • Ohio
      Nationwide Children’s Hospital
      700 Childrens Dr
      Columbus, OH 43205
      Contact: Lisa Moffitt
      614-722-8528
      lisa.moffitt@nationwidechildrens.org

      Principal Investigator: Jerry R Mendell, MD
      Status: recruiting
    • Oregon
      Shriners Hospitals For Children
      3101 Southwest Sam Jackson Park Road
      Portland, OR 97239
      Contact: Cathleen Buckon
      503-221-3471
      CEB@shcc.org

      Principal Investigator: Erika Finanger, MD, MS
      Status: recruiting
    • Pennsylvania
      Children’s Hospital of Pittsburgh of UPMC
      4401 Penn Ave
      Pittsburgh, PA 15224
      Contact: Jennifer M Monahan
      412-692-5176
      jennifer.monahan@chp.edu

      Principal Investigator: Hoda Z Abdel-Hamid, MD
      Status: recruiting
    • Pennsylvania
      Children’s Hospital of Philadelphia
      3401 Civic Center Blvd
      Philadelphia, PA 19104
      Contact: Contact: Michele Bergman
      267-425-2111
      BERGMAN@email.chop.edu


      Principal Investigator: Gihan Tennekoon, MD
      Status: recruiting
    • Texas
      Children’s Medical Center Dallas
      1935 Medical District Drive
      Dallas, TX 75235
      Contact: Holly Lawrence
      214-456-2463
      holly.lawrence@utsouthwestern.edu

      Principal Investigator: Susan Iannaccone, MD
      Status: recruiting
    • Utah
      University of Utah
      175 North Medical Center Drive East
      Salt Lake City, UT 84132
      Contact: Bria Jensen
      801-585-9399
      briaj@genetics.utah.edu

      Principal Investigator: Russell Butterfield, MD, PhD
      Status: recruiting
    • Virginia
      Children’s Hospital of the King’s Daughters
      601 Children's Lane
      Norfolk, VA 23507
      Contact: Terrie Conklin
      757-668-9356
      terrie.conklin@chkd.org

      Principal Investigator: Crystal Proud, MD
      Status: recruiting
    • Wisconsin
      Children’s Hospital of Wisconsin
      9000 West Wisconsin Avenue
      Milwaukee, WI 53226
      Contact: Marsha Malloy
      (414) 266-6792
      mmalloy@mcw.edu

      Principal Investigator: Matthew Harmelink, MD
      Status: recruiting

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