LEO Pharma A/S has launched the DELTA NEXT phase 2a trial to investigate delgocitinib cream in adults with mild to severe palmoplantar pustulosis (PPP), marking the first study of this topical pan-JAK inhibitor in the rare inflammatory skin condition. The randomized, double-blind, vehicle-controlled proof-of-concept trial aims to evaluate the efficacy and safety of twice-daily delgocitinib cream compared to cream vehicle.
Addressing Significant Unmet Medical Need
PPP is an uncommon, chronic, inflammatory, relapsing skin disease characterized by repeated episodes of sterile pustules alongside erythema, blistering and scaly skin on the palms and/or soles of the feet. The disease affects an estimated 0.01% to 0.05% of the population, with a higher prevalence in females and a mean age of onset ranging from 40 to 58 years.
"I've seen firsthand how PPP can severely disrupt patients' lives, making it painful to walk, perform activities of daily living and impacting their ability to work," said Dr. Robert Bissonnette, international coordinating investigator on the DELTA NEXT trial and Chairman at Innovaderm Montreal, Canada. "Despite the significant burden it places on patients, treatment options remain limited. There is a real and urgent need for effective therapies."
The condition is associated with a high patient burden, resulting in significant impairment of quality of life. Patients often experience pain, fatigue, and the condition can be triggered by factors such as smoking, infections, and stress. PPP is also associated with comorbidities including thyroid dysfunction and metabolic syndrome, and has been shown to have a greater impairment on work and daily life than plaque psoriasis.
Limited Treatment Landscape
Currently, there are no approved advanced systemic treatments for PPP in the U.S. or Europe. The condition is associated with complex T-cell activation patterns, which may explain why many biologics that target individual T helper cell populations have shown limited efficacy in clinical trials.
Pan-JAK Inhibition Strategy
Delgocitinib cream is a topical pan-Janus kinase (JAK) inhibitor that has been shown to inhibit the activity of all four JAKs, which are involved in inflammatory signaling. The therapy prevents the activation of the JAK-STAT pathway by blocking the signaling of several inflammatory cytokines, thereby suppressing the inflammatory cascade and preventing the downregulation of important barrier genes.
"The DELTA NEXT trial in PPP represents an exciting new chapter in the clinical development journey of delgocitinib cream," said Christophe Bourdon, Chief Executive Officer, LEO Pharma. "PPP is a disease with few treatment options that can severely affect quality of life. We are hopeful that this therapy could potentially provide much-needed help for patients suffering from this devastating condition."
Trial Design and Recruitment
The DELTA NEXT trial plans to recruit up to 135 patients with active, chronic, mild to severe PPP for whom topical corticosteroids are inadequate or inadvisable. Participants will be randomized in a 2:1 ratio to receive either delgocitinib cream or cream vehicle. Recruitment will take place across 40-45 sites in the United States, Canada, the United Kingdom, Germany, and Poland.
Established Safety Profile
Delgocitinib cream is currently approved in the European Union, United Kingdom, Switzerland, and the United Arab Emirates for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. The therapy is under review in other markets, including the United States.
PPP represents the first disease for which LEO Pharma will investigate delgocitinib cream since completion of the Phase 3 DELTA trials in chronic hand eczema. In 2014, LEO Pharma A/S and Japan Tobacco Inc. entered into a license agreement granting LEO Pharma exclusive rights to develop and commercialize delgocitinib cream for topical use in dermatological indications worldwide, excluding Japan.
