574 Preliminary results from an escalating dose cohort study of VT30, a topically formulated phosphatidylinositol 3-kinase inhibitor (PI3K), intended as a treatment for cutaneous vascular malformations associated with underlying PIK3CA or TEK mutations
نویسندگان
چکیده
Purpose: This report gives findings from an (ongoing) Phase 1b, escalating dose, clinical trial, assessing the safety and tolerability of VT30 Topical Gel as a treatment for venous, lymphatic mixed venolymphatic lesions skin (VM, LM VLM, respectively), driven by inappropriate activation intracellular PI3K. Methods: After giving informed consent completing screening evaluations that included confirmation underlying genotype (PIK3CA or TEK mutation), adult subjects with cutaneous VM, VLM were allocated to receive 4 weeks (wks) Gel, applied once daily 140 cm2 target area, lesion involvement. Four sequential, open-label dose cohorts 3 each (12 total) designed sequential completion follows: Cohort 1, 2 wks 0.12% (concentration strength) gel, followed final at 0.6%; 2, 0.6% 1.2%; 3, 1.2 % 2.3%; 4, full maximum tolerated feasible (MTD MFD, respectively) concentration. Results: 23 potential screened allocate total 12 - 7 positive PIK3CA mutation, 5 had mutation. Over treated in Cohorts 1 – topical gel has been generally safe tolerated. To date, patient assessments have reflected phenotypically heterogeneous group. Investigators reported changes consistent improvement vascular lesions. Adequate tissue-drug levels documented association pharmacodynamic readout suggesting local PI3K inhibition. No circulating drug detected plasma. Conclusions: Gel’s emerging profile is patients malformations skin, activation.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.583