Open-Label study of eteplirsen in Duchenne muscular dystrophy patients
Research type
Research Study
Full title
An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
IRAS ID
222670
Contact name
Francesco Muntoni
Contact email
Sponsor organisation
Sarepta Therapeutics, Inc
Eudract number
2016-000951-29
Duration of Study in the UK
2 years, 10 months, 19 days
Research summary
Research Summary
This is a phase 2 open label study to assess the safety, tolerability and pharmacokinetics of eteplirsen in young boys with Duchenne muscular dystrophy (DMD), who are amenable to exon 51 skipping. DMD is caused by a mutation (a change) in the gene (the part of cells that contain the instructions which tell our bodies how to grow and work) that makes dystrophin (a protein). Dystrophin is important for protecting muscles from stress and damage during activity. If a person has DMD, his body is not able to make enough dystrophin to protect his muscles.Symptoms of DMD may be present during the first year of life, but diagnosis is usually made between the ages of 3 and 5 years. About 100 boys with DMD are born in the UK each year. The risk of having a child with DMD is about 1 in every 5000 male births. There is no cure for DMD, but there are medicines and other therapies that can ease the symptoms.Eteplirsen is an investigational product being developed by Sarepta Therapeutics, Inc. which is designed to “skip” the missing part of the gene that make the dystrophin protein. “Skipping” over the missing area may allow the body to produce a shortened, but still working, form of the dystrophin protein. This study will test the effects of eteplirsen in young boys with DMD who have mutations that may be treated by skipping exon 51. About 13% of patients with DMD are amenable to exon 51 skipping.The study will recruit 4 patients in the UK between the ages of 6 months to 48 months. Procedures in this study will include physical examinations, body measurements, muscle function tests, blood and urine samples and weekly infusions. Blood samples will be collected for pharmacokinetic and safety assessments.Summary of Results
A trial to learn more about eteplirsen as a possible treatment for infants and young boys with Duchenne muscular dystrophy caused by certain genetic mutations Full trial title:
An open-label safety, tolerability, and pharmacokinetics study of eteplirsen in young patients with Duchenne muscular dystrophy amenable to exon 51 skipping A note about this summary:
This is a summary of the results of this clinical trial. It only shows the results of this trial. Other trials with eteplirsen could have different results. Researchers look at the results of many trials to understand which drugs work and how they work.
This summary describes the overall results of the trial. Results for each participant may have been different and are not part of this summary.
The trial started in August 2017 and ended in March 2021. This summary of the results was created after the trial ended on 10March2021 Why was this trial done?
This trial was done to learn more about a drug called eteplirsen as a possible treatment for infants and young boys with Duchenne muscular dystrophy caused by certain genetic mutations. Duchenne muscular dystrophy is often called “Duchenne” for short.
Duchenne is a rare genetic disease that affects mostly boys. People with Duchenne have a genetic mutation that limits their ability to make a protein called “dystrophin”. Dystrophin plays an important role in protecting and strengthening muscles. Without the ability to make dystrophin, people with Duchenne have muscle weakness in many parts of the body that gets worse with time.
There are different genetic mutations within the gene that makes dystrophin that can cause Duchenne. Researchers developed eteplirsen to try to help people with certain genetic mutations make a shorter form of dystrophin. For every 100 people with Duchenne, about 13 are thought to have a genetic mutation that might respond to treatment with eteplirsen.
Who took part?
Families of boys with Duchenne met with trial doctors to see if they could join. The trial doctors took a blood sample to learn which genetic mutations each boy had that caused Duchenne. Only boys who had Duchenne caused by certain genetic mutations could join this trial.
There were 15 participants in this trial. All of the participants were infants and young boys with Duchenne who ranged in age from 6 months old to 4 years old when they joined. There were 6 participants from the United Kingdom, 5 from France, 2 from Belgium, and 2 from Italy.
What happened during the trial?
All of the participants received eteplirsen. They started with a dose of 2 milligrams of eteplirsen for every kilogram of body weight. For example, a participant who weighed 10 kilograms started with a dose of 20 milligrams of eteplirsen. The dose was increased gradually over the next 10 weeks to 30 milligrams of eteplirsen per kilogram of body weight.
The trial doctors gave the participants a low dose at first and then increased it a little at a time so they could see how each participant reacted to treatment.
The participants received eteplirsen once a week intravenously (through a vein) for up to 96 weeks (almost 2 years). Some participants received eteplirsen through a needle (as an infusion into a vein). Other participants chose to receive eteplirsen through a “port”. A port is a device -- about the size of a large coin -- placed under the skin by a healthcare professional during a short procedure. If a person has a port, doctors can infuse a treatment into the port rather than directly into the vein. A tube from the port then carries the medication to the bloodstream. Once a port has been placed, it can be used for months or even years with proper maintenance. People whose medical treatment involves repeated injections, infusions, or blood sample collections might choose to have a port placed to avoid the need for regular needle pricks directly into their vein.
At the end of the trial, participants were asked if they would like to join an extension trial in which they would continue to receive eteplirsen. All of the participants joined the extension trial.
While each participant was in the trial for up to 2 years, the whole trial lasted just over 3.5 years because participants joined the trial at different times.
What was the main goal of this trial?
The main goal was to learn more about any medical issues the participants had during treatment, including any medical issues that the trial doctors thought might be related to eteplirsen.
What were the results?
These results describe the medical issues that the participants had during the trial that the trial doctors thought might be related to eteplirsen. These medical issues are called “adverse reactions”. These adverse reactions may or may not have been caused by eteplirsen. A lot of research is needed to know whether a drug causes a medical issue.
Some adverse reactions are considered “serious”. Examples of serious adverse reactions are those that are life threatening, cause long-term medical issues, or need hospital care for treatment.
Question: Did the participants have any serious adverse reactions? If so, what were they?
Answer: None of the participants had a serious adverse reaction in this trial.
Question: Did the participants have any nonserious adverse reactions? If so, what were they?
Answer: Three (3) of the 15 participants (20% of the entire group) had 1 or more adverse reactions that were not considered serious.
These were the adverse reactions that happened:
• Vomiting: This happened to 2 participants (13%).
• Flushing (the skin temporarily turns red and may feel warm): This happened to 1 participant (7%).
• Swelling in a small area: This happened to 1 participant (7%).
None of the participants stopped receiving eteplirsen because of an adverse reaction.
The websites listed at the end of this summary have more information about other medical issues that participants had during the trial.
How has this trial helped?
The results of this trial helped doctors, researchers, and health authorities learn more about eteplirsen as a possible treatment for infants and young boys with Duchenne caused by certain genetic mutations. Clinical trials like this are important to help researchers understand which treatments work best and are safest for patients.
At this time, additional clinical trials with eteplirsen are ongoing.
This was a Phase 2 trial. Drugs tested in Phase 2 trials have already been studied in small numbers of participants to learn whether they can be given without causing severe side effects and which dose or doses should be used. Participants in Phase 2 trials help researchers learn more about how a drug works or what the best dose of a drug might be. They also help researchers learn more about the side effects people might have after taking the drug. If a drug is being studied as a treatment for a rare disease such as Duchenne, results of a Phase 2 trial might be used to seek approval of the drug from health authorities.
Where can I learn more?
You can find more information about this trial on the websites below. If a report of the results is available, it can also be found there.
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DouFFm-2FZqrUn2jjUD5TieZBfigX0bV4wUGi1E343XhAvX3yVhzvwFNscFn-2FUC0vTFjdeH_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YInkVLSjAq9jbhWS0uaSg3jRv1J0medNuXWx2almUc6mf5tFGufLVt1K9ipXfWiDoYCqiT07PAX-2FLJLtaSl2nrzvGWIkrmVAobI327DYO2XjSXBN4-2FqyCpyqMubnqXNn2iuAi7UEQcyXf-2B0jRY-2BYtqLpP0nfSiRcI14z46cEQBMfw-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C173863162fc94fad3e6908da011912fd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637823504461092693%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=l2RSstA%2FL1Mvwz3Z1IHGuj1FiWlpIM5Ss13rC85QYwo%3D&reserved=0 – On this website, click “Home and Search”. Then type 2016-000951-29 in the search box and click “Search”.
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DouFFm-2FZqrUn2jjUD5TieZBfigX0bV4wUGi1E343XhAv3xNcRXMCo3uktdpJWyu-2B6nlbR_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YInkVLSjAq9jbhWS0uaSg3jDGAPC8CTu3L6f6VLHsMsBigvgZpbf3s1THv4-2BUx1BtF4GMCVkDub-2BHedgO-2B61GvyC-2B0EftEFmLUghW12vulT3nFyUPRXsCurgEvSzfwv7LOvwdJFTR2bZ2BwKk4e8NUcv87-2FDedUnsfwP-2FUzgx0KcA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C173863162fc94fad3e6908da011912fd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637823504461092693%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=Y8cq8IkgC4ONWZ0QJdSNYkDJ3VI2xrwWujefB2L5pvU%3D&reserved=0 – On this website, type NCT03218995 into one of the search boxes and click “Search”.
You can find more information about Duchenne and genetic mutations at the websites below.
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVgpVFNT9vpez1fQcC5F5vRCJJXqhcWAmHH3bYwL3hLyqGa4_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YInkVLSjAq9jbhWS0uaSg3jUIHFqO-2FRzYRYuZ1bEugtS8Whc0lAfDocu9AM9CawSp-2BuYKxiK-2F9e7FQDf5Dbq0MBqoFCL-2Bah1ZBz3EW4Axbc3JfcpeNsq-2FJ5NclAN-2BAitRwWNezEwClB69zfI1aa37czmXvEcr3l6JcVRtrmdI6WTA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C173863162fc94fad3e6908da011912fd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637823504461092693%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=RQUDNyTzUL11EzcHikZFAYnn9KgmF352Ljsrek%2FPU0c%3D&reserved=0
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQ1dIzpNF-2BEoyfFPyVvyHVxdbKSp4fhLBiOJQd2j9UmJU7RL_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YInkVLSjAq9jbhWS0uaSg3jegbZySEY9xztf6xvVqqr4J-2B7CD3FQYGBjnkVDNeVdDQp-2Fz96PGL3cfzThs0tkDkXSvUJ6FgpUzNkQMSBrlwP2O-2FJicpw5s0uFW935zsfFK-2BDmjL3DsnLY2-2BZtNmHj2ViQMw59W7vLCbIXOnP4nm8vA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C173863162fc94fad3e6908da011912fd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637823504461092693%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=0WaK6ukvV73eX3vFOy94q%2FsPs6vONB%2FThmA8vXJKqE4%3D&reserved=0
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQOX1-2FJPDtFm54iXMuPo5wC7bfhG9F-2FQk3844C3p1VREJ9BdM9eFty7IKGpbbbRsc0eCCqDeUTvbWoE-2FTEwSv2ctiI7btNZW3xhwHt-2BV1WYCM6Iq_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YInkVLSjAq9jbhWS0uaSg3jNZr0HFGyCwnNLJQnsZZGRK-2BKctZ1X76xr6uIwQA9tmsIA97oU5fN0ge6-2FeQojSl5Z6zA1JWHTqH-2F0-2B3GALfA7hQiBhUFMTn8out5q00hFn3Rli3286asXLwCUy97kkirJo5LNQBCMlY27mQXM2cG6w-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C173863162fc94fad3e6908da011912fd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637823504461092693%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=jvihY0CwYxvnZCEOunQx4M9otgEx3sinZZwL5SAl6Rw%3D&reserved=0
Here is some additional information about the trial:
This is the ID for the trial protocol: 4658-102 This is the company that sponsored the trial:
Sarepta Therapeutics Inc.
Here is the sponsor’s contact information:
Phone number: +1-800-690-2003
Email address: SareptAlly@sarepta.comREC name
London - Hampstead Research Ethics Committee
REC reference
17/LO/0788
Date of REC Opinion
22 Jun 2017
REC opinion
Further Information Favourable Opinion