Clinical Trials & Studies

siRNA Trial

First-in-human Mutation-targeted siRNA Phase 1b Trial of an Inherited Skin Disorder
(Molecular Therapy 24 Nov 2009)

Also see Published Research Articles for additional publications on Pachyonychia Congenita research and clinical trials.

Current Clinical Trials

TD101sd (a self-delivery siRNA)

Topical Rapamycin


Patients must be in the IPCRR to qualify for Clinical Studies sponsored by PC Project.




PC Project is moving steadily forward in "translational research" to take laboratory discoveries into treatment for patients in numerous studies and clinical trials.

Selecting Patients for Clinical Trials and Studies

As we move forward in developing treatments for PC, patients are selected from the IPCRR. This is a general idea of how the process works:

  • A scientist has completed basic research (including chemical, toxicology and other work)  to identify or develop a possible treatment. PC Project often supports this basic research.
  • PC Project collaborates with the scientists and qualified physicians to gain necessary approval to test the treatment on patients. Every jurisdication has regulations regarding clinical studies. This may be a university (known as Institutional Review Board or IRB approval), or a federal government  (such as the Federal Drug Administration or FDA approval in the USA).
  • The IPCRR database is checked to identify patients with the gene or mutation that the drug targets. This may be any of the five PC genes or it may be a specific mutation found on a specific PC gene. The locality of the patients is mapped to determine where sufficient qualified patients are located to conduct the study. Whether or not all family members have enrolled in the IPCRR may influence where a study can be held.

2013 Studies and Clinical Trials

siRNA sdTD101. A pre-IND meeting with the FDA was held on May 1, 2013 for the next siRNA clinical study. The initial siRNA trial (TD101) was conducted in 2008. Since that time, work has been progressing to enhance the drug for more effective delivery. Also, developing delivery methods other than hypodermic injections has been a high priority. TransDerm has produced microneedles under the necessary GMP standards for human use. Also, TransDerm has explored the use of another array device which may have potential. Dr. Leonard Milstone (Yale University), Dr. C. David Hansen (University of Utah) and Dr. Alan Irvine (Our Lady's Hospital for Sick Children, Dublin, Ireland) are preparing to administer the trial in their areas as approvals are obtained.

Topical Rapamycin. A pre-IND meeting with the FDA was held April 15, 2013. In the next months, the final IND will be filed seeking FDA approval for a clinical trial using topical rapamycin. Pfizer has donated the drug product (with a value of approximately $500,000) for the trial. TransDerm, our biotech partner, has completed the toxicology studies and other pre-trial work for filing the IND. Patients in the IPCRR who qualify for the trial will be recruited. Joyce Teng and Jean Tang (Stanford University) are preparing to administer the trial as approval is obtained.

Cyst Histopathology. Following the August 2011 Patient Support Meeting, a small group of researchers focused on the needs of PC-K17 patients. Very little is known about cysts in PC or in other similar disorders. There is no basic science information on the mechanisms involved in cyst formation and details of the biological pathways are unclear. The group recruited one of the leading histopathologists, Phillip LeBoit, of the University of San Francisco to study cysts from PC patients. While basic science isn't a drug or treatment, it is one of the most necessary building blocks to research progress.

So far, twelve cysts have been received at UCSF. More samples are needed for the study to produce meaningful data. We invite all patients in the IPCRR who are having a cyst removed to please contact PC Project so that we can collect the sample as needed for the study.

Nail Removal Survey. In the Fall of 2012, physicians asked PC Project to collect data from patients in the IPCRR who had nails removed. There are many questions regarding both the methods of nail removal and the outcome for PC patients. Twenty-five patients responded and the data is being analyzed. A follow-up study is planned.

Pain Study. At the 2011 Patient Support Meeting, pain specialist Barbara Hoggart, MD (Solihull Hospital Pain Management Clinic, UK) and several colleagues conducted extensive written and physical testing of 40 patients. Since that time, pain specialists and statisticians have been working to analyze the information collected. They have confirmed that PC results in neuropathic pain for some patients as well as * pain. A poster summarizing the findings was presented at the prestigious American Acadamy of Pain Medicine Annual Meeting in April 2013. The abstract will appear in the journal Pain which is the highest impact journal for pain in the world.

Other Studies and Clinical Trials

OCT Imaging. In 2012, one PC patient and patients with other similar disorders were studied using the OCT method of imaging at Mt Sinai Hospital in New York City by Leonard M. Milstone, MD (Yale University). For clinical trials, it is essential to have tools that measure changes to prove safety and efficacy of drugs being tested. The OCT imagining in skin may provide the needed tool.

Topical Gabapantin. In 2012, six patients participated in an off-label study using topical gabapantin under the direction of C. David Hansen, MD (University of Utah, Department of Dermatology). The study found that topical gabapantin had no measurable effect on pain in PC patients.

Nail Histopathology. At the 2011 PC Patient Support meeting, PC patients provided nail clippings and nail photos for Adam Rubin (University of Pennsylvania, Department of Dermatology). The analysis is completed and a publication is being prepared.

PC Quality of Life. Peter Hull (Department of Dermatology, University of Saskatoon) recognized the need for a specialized Quality of Life Index for PC. 125 patients and more than 100 normal controls participated in the clinical study to validate the PC QofL tool. Statistical analysis has been completed to further validate the data and a publication has been prepared.

Bioptigen Imaging Study. Roger Kaspar of TransDerm arranged for special imaging of a patient at Bioptigen headquarters in North Carolina. In order to show efficacy of treatments, scientists must find tools which measure or image changes in PC skin. The results of this study did not provide the hoped-for depth of image.

GeneCream. In 2008, Roger Kaspar (TransDerm) and dermatologists from Stanford University tested delivery to PC plantar skin using GeneCream. A new imaging camera system developed by the Christopher Contag laboratory at Stanford University was used to view delivery in the skin. The study showed that PC plantar skin was more porous than skin of a normal control patient.

Ultrasound. Eli Sprecher, MD, PhD (Department of Dermatology,Tel Aviv Sourasky Medical Center, Israel) and Diana Gaitini, MD conducted ultrasound studies on patients with PC and patients with other callusing disorders. Their work visually identified blisters under the callus in PC patients which were not present in other disorders. A publication will be available in 2013.

Statins. Based on research in 2008 by W.H. Irwin McLean, PhD  (University of Dundee, Scotland) showing that statins may impact keratin genes (see sidebar for publication), Peter Hull, MD, PhD (Department of Dermatology, University of Saskatoon) began treatment of four PC patients using an oral statin. Over several years, the study results showed some improvement in pain and additional patients were studied by Eli Sprecher, MD, PhD (Department of Dermatology,Tel Aviv Sourasky Medical Center, Israel). The Israeli patients did not experience an improvement in pain. A third study is on-going in Alberta, Canada.

siRNA TD101. An FDA-approved clinical trial using a targeted siRNA (TD101 from TransDerm) was completed in 2008 (see sidebar for publication of this Phase 1b Clinical Trial). Drs. Sancy Leachman, C. David Hansen and Mark Eliason administered the drug. The trial was successful in clearing an area of callus and pain, but the delivery of the drug by hypodermic needle was unbearably painful as the sidebar video shows. Following the trial, researchers in the IPCC began efforts to improve the siRNA drug as well as to develop more patient-friendly delivery methods.

Rapamycin. Research on the drug rapamycin conducted at TransDerm showed an effect on the mTOR pathway which includes some of the keratin genes. During 2006 and 2007, oral rapamycin was tested in three PC patients  (see sidebar publications). Improvement in pain was noted by the patients, but side effects of the drug prevented continuation of the study. Since then research has continued to produce a topical form of the drug to allow treatment without side effects and to secure drug product (see 2013 Clinical Trials).

Dysport/Botox. In 2006, Sancy Leachman, MD (Department of Dermatology, University of Utah) and Mary Schwartz, PC Project traveled to Upsalla, Sweden to view the administration of botulinum toxin (brand names Dysport or Botox). The treatments were done under anesthesia in the surgical center at the Upsalla University Hospital under the direction of Carl Swartling, MD and Anders Vahlquist, MD, PhD. Some patients repeat the procedure and find it effective in reducing pain for several months. There is no universal approval for this treatment. Cost estimates in the USA would be close to $100,000 per treatment. Efforts continue to be made to develop a topical form of the drug to reduce costs and extend the studies.

Imaging study. At the Patient Support Meeting in 2005 held near Buffalo, NY, Lucid Imaging Systems brought their equipment to test imaging in skin (not the surface but into the skin). A number of patients had images taken to see if the camera would image through the callus. Additional adjustments to the equipment were proposed and later delivered (2009 Delivery Grant) but the technique has not fully been optimized to provide the necessary results.

Topical retinoid. Since oral retinoids have side effects which are problematic for most patients, in 2005 a topical form of Tazorac was conducted. The topical form did not prove effective in PC patients treated.