10 Clinical Trials for Various Conditions
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".
This study evaluates the safety and efficacy of QTORIN 3.9% rapamycin anhydrous gel in the treatment of adults with Pachyonychia Congenita. This study includes a screening period, baseline period and 6-month treatment period.
VALO-2 is a multicenter, open-label extension (OLE) study enrolling patients with genotyped keratin mutations KRT6A, KRT6B and KRT16 who were previously treated with investigational PTX-022 during the VALO study. The purpose of the OLE study is to investigate long term exposure to investigational PTX-022 and evaluate safety and efficacy data. A sub-study is included to evaluate safety and efficacy of patients with genotyped keratin mutations of KRT6C and KRT17 not previously treated with investigational PTX-022.
This study evaluates the safety and efficacy of PTX-022, topical rapamycin, in the treatment of adults with moderate to severe Pachyonychia Congenita. This study includes four-parts, and if a participant completes all parts, the participant will have received at least 3-months of PTX-022 treatment.
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.
A study to evaluate safety and efficacy of topical sirolimus to treat plantar keratoderma in adults with PC. Subjects may receive either placebo or treatment with at least 1 foot receiving topical sirolimus at some time. For certain phases of the study treatment assignment to the right and left foot will be randomized in a double blind fashion. Blood levels will test systemic absorption of sirolimus. Other safety and efficacy measures will be taken through the 39-week study duration. Funding Source - FDA OOPD
Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder affecting the nails, skin, oral mucosae, larynx, hair and teeth. Pathogenic mutations in keratin K6a, K6b, K16 or K17 act via a dominant negative mechanism, leading to manifestations of the disease. The most disabling PC symptom is a painful plantar blistering and keratoderma that requires use of ambulation devices in more than 50 percent of patients. Despite our understanding of the molecular basis of PC, current treatment is limited to mechanical removal of the thick calluses, non-specific topical keratolytics, and oral retinoids, none of which alleviates blistering or plantar pain satisfactorily. A public charity, PC Project, has been founded to support the development of treatments for PC (www.pachyonychia.org). In collaboration with this charity, a small company, TransDerm, Inc., has developed a small interfering RNA (siRNA) that specifically targets a mutation in one of the PC keratins, K6a. As this siRNA targets a single nucleotide mutation, it will only be effective against PC subjects harboring this specific mutation. There are currently only six known patients who carry this mutation in the International Pachyonychia Congenita Research Registry, but three of these patients live in Salt Lake City (a mother and two of her children). We propose to perform a Phase Ib clinical trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation. We will complete treatment of the adult patient prior to recruitment of the minors.
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.
Adult participants will apply a broccoli sprout extract-jojoba oil compound to one arm every night under occlusion for 1 week. Jojoba oil alone will be applied to the other arm. At the end of 1 week, a 6mm punch biopsy will be taken from both arms and analyzed via polymerase chain reaction (PCR) and immunohistochemistry for differences in various skin proteins.
The ichthyoses are a family of genetic skin diseases characterized by dry, thickened, scaling skin. Dermatologists estimate that there are over twenty varieties of ichthyosis, with a wide range of severity and associated symptoms. This registry is designed to identify people in the United States with the ichthyoses and other related disorders and to collect information about their skin ailment and how it has affected them. The database is available for review by approved research applicants. The registry is confidential and provides investigators a way to share information about studies and trials with potential participants while maintaining participants' privacy. Although the Registry is closed to new enrollment, it is still maintained in order to provide information related to understanding the diagnosis, pathophysiology, and treatment of ichthyoses. Support for studies continues and inquiries from investigators are welcomed.