To read PDF files, click on the icon above to get
the free Adobe Reader.

Clinical Trial for TD101
TD101 is an siRNA designed to target one of the mutations which cause Pachyonychia Congenita. Following several years of development, the US FDA granted the proposal for a Phase 1b clinical trial in PC patients.

News Release January 2008

Stanford University Blog Regarding TD101

TD101 Clinical Trial - An Essay by Mary Schwartz
March 2007. Update. Thank you all for your thoughts, prayers, messages and kind encouragement. This is an important trial. There are other studies and trials which are on-going. We intend to do everything possible to find therapies that work to relieve PC pain and to lesson PC problems.

Eight weeks of the TD101 clinical trial have been completed. There are six weeks (12 injections) to go. Everything is going well for the 'safety' aspects (please read the entire essay below). The injections were too painful to bear, so some local blocks and pain medications are being used. Unfortunately, this results in a loss of two full days each week for those receiving the injections. As outlined below, we are pleased to be at this point in the progress towards therapies for PC.

February 2007. Many caring and interested friends are asking 'how's the trial going?' Over the last weeks, I have struggled to find a way to explain how important this trial is and how impossible it is to answer the question. I will try.

A Phase 1b Clinical Trial is a 'safety' trial. The purpose of the trial is to not to demonstrate that the drug has a good effect (reduces blistering for example), but rather it is to prove the drug has no harmful effect. So to answer honestly, the trial is highly successful! There have been no negative effects from the drug!

To prove that a drug is safe is a major task. The manufacture of the drug had to be according to GMPc standards, the storage of the drug has to be under special conditions, the testing of the drug in a non-human species had to be completed and those tests set the limit (i.e. 28 injections) for the human trials. The drug for tesing in the lab may cost $5,000 or $15,000 per gram. The same drug prepared for testing on humans costs in the millions of dollars.

It is a major task for those in the trial as well. For the patients, it requires from 2 to 3 hours, plus travel time, twice a week to go to the hospital for the injections. Before the injections, baseline testing is necessary which involves a complete physical, urine test, blood tests, pregnancy tests and many other tests. Quality of Life questionnaires must be completed each time. Careful measurements and examination is done every visit of not only the injection site, but nails, tongue, skin and other areas. Also, extensive photographs are taken once each week adding an hour or more to the visit. In addition, the patients complete the on-line pain diary twice a day. And, all of these measurements and tests are to see that there is no harmful effect from the drug.

Also, the trial is called a 'split-body' study and the drug is injected in one foot and a placebo injected in the other foot. And, no one involved knows which is going in which foot. Both injections are extremely painful. The entire process in physically and mentally exhausting partly from dealing with the time, all the different factors, the pain -- and the sense of responsibility for everyone.

However, I can sense that those asking are really wanting to know 'does it help PC.' We don't really know whether we'll know that at the end of the trial. However, if we do know that, it will almost certainly not be the patients or even the physician giving the injections who will be able to tell that there is an effect. Why? (1) the area that is being treated is about the size of a large walnut and (2) the effect will be on the cells. No one knows how long it takes cells to move from the lower layers of the skin to the surface. Will 14 weeks be enough time? Etc.

There is a very small possibility that the trial will not only prove safety (which is the purpose and hope for the trial), but also prove that the drug has an effect not only in the lab, but also in humans. So to try to look for that effect at the cell level, the patients are collecting shavings from the treated area and two other remote areas from each foot twice each week. PC Project is shipping these samples on dry ice to TransDerm. The scientists there have developed sophisticated testing methods to be able to look at the cells and measure the specific levels of the mutation and normal gene for this mutation. There may be no result detected because (a) the drug may have no effect in such a short period of time or (b) the affected cells may not reach the surface in the short period of time so that they are not collected in the shavings.

So, 'how's it going?' or 'is it working?' YES! Thanks to dedicated patients, physicians and scientists. This is a major breakthrough. We'll be thrilled with 'no negative' effects. Daily researchers are working to develop other delivery methods that can spread the drug to a wider area and not be administered via painful injectsion. Daily researchers are testing other types of drugs (some already approved for humans) to measure effects on PC. So much is happening for this rare disease.

At PC Project we are focused on this ultra, ultra rare disease pachyonychia congenita. However, we know and are thrilled that our success for PC will mean major success for other disorders as well. I hope this 'essay' gives you an answer. Your interest, your support, your prayers are gratefully appreciated by all involved. Thanks so much.