Efficacy and Safety of 1% Progesterone Gel to the Forehead on Ocular Chronic Graft-versus-Host Disease

Abstract Background There is no FDA-approved treatment to date and current therapeutic options for ocular chronic graft-versus-host disease (oGVHD) are limited. Forehead application of 1% progesterone gel provides corneal antinociception in preclinical models, suggesting it may be useful in alleviating ocular irritations. Objectives To evaluate the efficacy and safety of 1% progesterone gel in moderate-severe symptomatic oGVHD. Study Design In this single-center, sponsor-initiated, prospective, exploratory, randomized, double-masked, placebo-controlled phase II clinical trial, 33 patients with oGVHD following allogeneic stem cell transplantation were enrolled. The inclusion criteria included a National Institute of Health consensus score of 2 or higher; moderate to severe ocular discomfort level; and on stable immunosuppression regimen. Twenty one out of the 22 patients in the progesterone arm and all 11 patients in the placebo arm completed the course of twice daily forehead drug application for 10 weeks. The changes from baseline of self-reported ocular symptom scores and physician-recorded cornea fluorescein staining scores were analyzed using mixed-model repeated measure regression model on intended to treat population. Results Among the 33 patients, median age was 66 (range, 24-75) years; 12 were women and 21 were men. At 10 weeks, there was significant reduction in ocular symptoms from baseline in the progesterone group compared to the placebo group in symptom frequency (-30.7 vs -2.2, P Conclusions Forehead application of 1% progesterone gel significantly improved ocular symptoms and signs within 10 weeks. It appears to be a safe and effective new therapy for oGVHD, and a novel mechanism for neuro-axis drug delivery. A multi-center phase III clinical trial is planned for further validation.