Edimer: Clinical trials are an important part of developing new medical treatments. They help doctors and scientists determine if new drugs are safe, effective, and prescribed at the correct dosage. The newborn XLHED clinical trial is a Phase II study evaluating EDI200. Trials conducted in Phase II determine how well the new drug meets the goals of the study for safety, effectiveness, and optimal dosing to achieve the best results.
Edimer: Baby boys between two and 14days old and who have had genetic testing confirming a diagnosis of XLHED are eligible to participate.
The process of skin, gland, tooth and hair development is highly controlled by the body - both time and location are very important. In humans, most of the groundwork for developing full functional sweat glands, hair and teeth (both primary and adult) is started and nearly completed at the time we are born. That is why it was such a remarkable finding in mice and dogs with XLHED that EDI200 treatment of newborn pups could have such a dramatic impact in these structures. We seek to understand how the windows for EDA-A1 (or EDI200) activity might be extended in humans, and whether there is a treatment that could reopen these windows of biological activity in adult patients.
However, at the moment, we believe the best benefit will be when EDI200 is given during the newborn period, very early within the first two weeks after birth. We have so much to learn and are very excited to pursue all the ways that may provide real benefits to XLHED-affected patients at all ages.
We recognize that a lot of carrier girls also have symptoms of XLHED. The boys tend to have more consistent and similar symptoms that are typically more severe. Therefore, the first clinical study will only enroll newborn boys as they have the best opportunity to see a benefit in receiving EDI200. Once the safety of EDI200 is confirmed, future studies may involve all XLHED-affected patients.
Edimer: Studies of fish, mouse and dog models of XLHED tell us that the protein that EDI200 replaces, EDA-A1, has a very important early role in the development of sweat glands, teeth, hair follicles, skin, etc. EDI200 functions very well in filling the role for missing EDA-A1 for these parts of the body as long as they still are "receptive" to being stimulated to grow. All the data we have to date suggests that the window for "receptivity" may end early in life, shortly after birth humans. This means that we believe the best benefit will be if EDI200 is given during the newborn period, very early within the first two weeks after birth.
Also, we have been looking very hard to see what role, if any, EDA-A1 may play after the newborn period. This could be in stabilizing glands (like those that produce mucous and tears), or even enhancing the growth of the hairs that are already present in XLHED-affected children. There may be a subset of people affected by XLHED who have specific gene mutations (a change in a gene) that may respond to ongoing EDI200 treatment, even if started later in life. Proving there is meaningful benefit has been hard to come by but we are continuing in this effort.
Edimer: Families who are interested in participating should contact genetic counselor Carrie Milliard at 207-662-6712 and she can provide further details.
You are also welcome to contact Edimer directly:
Edimer: It is helpful if you contact one of the above people as early as possible in your pregnancy, so we can answer any questions you may have and provide you with as much information as you need to consider participating in the clinical trial. Additionally, it is helpful for the study team to get information about your family’s history with XLHED and help to arrange any travel or operational details that might be required. Contacting a member of the team is not a commitment to participate in the clinical trial -- participation is always voluntary. You can choose not to participate at any time and for any reason. Not participating will have no effect on the current medical care you or your family are receiving or may receive in the future.
Edimer: Five doses of EDI200 are given over the course of two weeks. EDI200 is delivered by an intravenous infusion. EDI200 is only available at one of the clinical study sites listed below.
Edimer: Currently, we have the following sites in the United States and Europe:
· United States, California - University of California, San Francisco
· United States, District of Columbia – Children’s National Medical Center
· United States, Missouri – Washington University School of Medicine
· Germany – University Hospital Erlangen, Bavaria
· United Kingdom – University Hospital of Wales, Cardiff
The list of clinical sites may change, for the most up-to-date list and for further contact details, visit the clinical trials website.
Edimer: The current protocol includes enrolling 6 – 10 newborn boys in this Phase II clinical study of EDI200.
Edimer: We were pleased to share with the NFED and XLHED communities that the first baby was enrolled in the clinical trial in September 2013 and he successfully completed dosing with EDI200.
An independent committee that monitors the safety of the babies in the study has given the green light to enroll the next baby boy. We are unable to provide an update with each baby that is enrolled, however, we can share that the study is actively enrolling and moving forward.
Edimer: In the first Phase 2 study to involve XLHED-affected newborns, we will follow all aspects of growth and development as well as health issues specifically related to XLHED. Some testing will be done soon after EDI200 is given and some results are best collected later. It is important to remember that seeing a change in one baby will not be enough to be sure of an EDI200 effect. It is very important for us and for the XLHED community that when we share study results they are accurate and well documented.
Edimer: The window of treatment is very small, between two days and 14 days old. Additionally, while we have clinical sites across the United States and Europe, it is likely that travel will be required for families to participate. Therefore, whenever possible, it is very important for families to be in touch with a member of the team before the arrival of their baby boy so arrangements can be made. If you decide to participate in the clinical trial all costs associated with traveling to and from staying at the clinical study site will be covered.
One of the most helpful pieces of information to have is genetic confirmation that the baby boy’s mother is a carrier of XLHED. This can be done by a genetic test where the mother has a small tube of blood drawn and sent to a laboratory for XLHED genetic testing. If you need assistance with arranging or the cost of this genetic test, you may be eligible for free genetic testing through the XLHED Global GeneScreen.
Learn more details or contact genetic counselor Carrie Milliard.
Edimer: We have data regarding safety and adverse side effects from a number of studies that are outlined below. This is the standard for all new drugs that are being developed for human patients.
1. Animal models of XLHED (XLHED-affected newborn dogs and mice).
Over the last decade, dozens of puppies and hundreds of mouse pups have received EDI200. No adverse reactions related to the new drug were demonstrated in these animals. The puppies received EDI200 in a manner consistent with how it will be administered to babies (same number of doses and by intravenous infusion). These animals developed well into adulthood and are still being followed.
2. FDA required toxicology (drug safety) studies in unaffected animals.
The FDA requires these types of studies in two different animal species before any drug can be given to humans. The two animal species tested with EDI200 in newborns were mice and dogs. The animals in the FDA-required testing were not affected by XLHED. These newborn animals were given doses of EDI200 far in excess of what would be given in the human studies. This is called the margin of safety. The results of these studies did not demonstrate any consistent drug-related side effects. All of this data was sent to the FDA for review prior to being allowed to start the human studies with EDI200.
3. XLHED adult safety study in humans.
Six XLHED affected adults (four men and two women) were dosed with EDI200 in the first human safety trial late in 2012 through early 2013. Each of the six subjects received all five doses of EDI200 they were supposed to, the same number as neonates will receive. The study is now completed and all are doing well.
The data from this study has been reported to an independent Data Safety Monitoring Board and it shows that when EDI200 is administered by slow IV infusion, the only drug related adverse effect was some irritation at the injection site. This was a rare finding that cleared within 24 hours.
Given these results, we do not anticipate any significant EDI200-related adverse effects in newborn baby boys. Of course, we will be extremely vigilant in following these patients through the use of laboratory blood tests and frequent vital sign and clinical monitoring. Unanticipate deffects (like allergic reactions)arealways a possibility, and the experts at the clinical site are available to assess and treat appropriately.
Ectodysplasin–A1 (EDA-A1) is a protein that occurs naturally in the body. When a person is first growing and developing as a baby, EDA-A1 has a very important job, which is to signal the normal growth of hair, teeth, skin and certain glands like sweat and mucous glands. In people who are affected by XLHED, EDA-A1 is missing due to an alteration in the EDA gene.
EDI200 is a synthetic version of EDA-A1 being developed by Edimer Pharmaceuticals, Inc. EDI200 given to newborn dogs who have XLHED can restore the growth of their teeth, skin structures and mucous glands. By replacing the missing EDA-A1 with EDI200 while a baby with XLHED is still growing and developing, Edimer hopes to provide a life-long improvement in their health.
Edimer offers free genetic counseling and testing to those who qualify, including women 18-40 years of age who suspect they may be carriers for XLHED and newborn boys up to 28 days old. Learn more.