Clinical Research Directory

Safety, Tolerability, and Efficacy of Oral KM-023 in Adult Patients With Pachyonychia Congenita (pEDD-PC)

The goal of this clinical trial is to learn if KM-023 is safe and well tolerated in adults with Pachyonychia Congenita (PC). The study will also explore whether KM-023 may help reduce pain, improve mobility, and lessen the impact of PC on participants' daily lives. The main questions it aims to answer are: What medical problems or side effects do participants experience when taking KM-023? Does KM-023 improve participants' ability to walk and perform physical activities? Does KM-023 reduce pain, especially pain in the soles of the feet? How does KM-023 affect the severity and impact of PC symptoms? Researchers will evaluate changes during treatment compared with participants' condition at the start of the study. The study will include 10 adults with genetically confirmed PC who have visible painful calluses on the soles of their feet. All participants will receive KM-023; there is no placebo group. Each participant will be involved in the study for up to 170 days, including screening, treatment, and follow-up.

Epidermal Growth Factor Receptor Inhibition for Keratinopathies

Epidermal growth factor receptor (EGFR) signaling plays a key role in regulating epidermal cell proliferation, survival, and differentiation. Keratins form a scaffold with epidermal desmosomes that involves ErbB/ EGFR signaling and keratin deficiency makes keratinocytes more sensitive to EGFR activation. Erlotinib, an EGFR inhibitor, was approved 20 years ago for cancer treatment and is generally used at 150 mg daily in adults \>50 kg. While gastrointestinal and cutaneous side effects commonly occur at doses of 150 mg, adverse events occur less often at lower doses. We first reported erlotinib as effective for Olmsted syndrome, a rare hereditary EDD with painful PPK that results from variants in TRPV3. Erlotinib is now the treatment of choice for children and adults with Olmsted syndrome. Erlotinib is thought to inhibit formation of a complex that includes TRPV3, EGFR, and its primary skin-based ligand, TGF-a, which in turn regulates keratinocyte proliferation and differentiation. High-throughput screening to identify compounds that stabilize keratin filaments have also pointed to the EGFR pathway for targeting. Reviews and recent case reports have suggested the benefit of erlotinib for PC, Given these preliminary data, we hypothesize that EGFR activation is a characteristic feature of keratinopathies. Further, we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients. For those who experience pain, particularly from plantar involvement, we predict that erlotinib therapy will improve mobility and pain. Finally, we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response. We will look specifically at the impact on differentiation vs. hyperproliferation and barrier function, as well as the immune modulatory effects of the erlotinib using a multi-omics approach.

A Study Evaluating the Safety and Pharmacokinetics of QTORIN Rapamycin 3.9% Anhydrous Gel in the Treatment of Adults With Pachyonychia Congenita

PALV-08 is a multicenter, open-label treatment (OLT) study enrolling adults with Pachyonychia Congenita (PC) with genotyped keratin mutations KRT6A, KRT6B, KRT6C or KRT16 who were previously enrolled in the PALV-05 (VAPAUS) trial. The purpose of this OLT study is to investigate the safety of long term exposure and pharmacokinetics (PK) of QTORIN rapamycin 3.9% anhydrous gel or "PTX-022".

International Pachyonychia Congenita Research Registry

International Pachyonychia Congenita Research Registry (IPCRR) is a patient registry for those suffering from Pachyonychia Congenita (PC). PC is an ultra-rare extremely painful skin disorder that causes painful blisters and callus on feet and sometimes hands, thickened nails, cysts and other features. The IPCRR consists of a questionnaire, patient photos, optional physician notes from telephone consultation to validate questionnaire and free genetic testing.