DELTA 2 Trial Shows Delgocitinib Cream Safe with Minimal Systemic Absorption for Chronic Hand Eczema

Image Credit: © Te Whatu Ora Health New Zealand; DermNet

A poster¹ from the 2024 Elevate-Derm West Conference reported the systemic exposure and safety of delgocitinib (LEO Pharma) cream in adults with moderate to severe chronic hand eczema (CHE). Findings are based on data from the phase 3 DELTA 2 (NCT04872101) trial.²

The DELTA 2 trial, a pivotal phase 3 clinical study, aimed to further assess the safety and systemic absorption of delgocitinib cream 20 mg/g in adults with moderate to severe CHE, particularly examining systemic exposure after topical application and its effect on various laboratory parameters.

The randomized, double-blind, vehicle-controlled study with a 2-part design enrolled adults aged 18 to 84 with moderate to severe CHE. Patients were randomized in a 2:1 ratio to receive either delgocitinib cream (20 mg/g) or a cream vehicle. The treatment was applied twice daily for 16 weeks.

The study focused on systemic exposure by analyzing pharmacokinetics. Blood samples were collected 2 to 4 hours after delgocitinib application at weeks 1, 4, and 16, with a lower limit of quantitation of 5 pg/mL.

For each sample, researchers measured parameters like maximum concentration, time to reach maximum concentration, area under the curve, and half-life. Systemic safety was evaluated by measuring changes in laboratory parameters, including blood counts and lipid profiles, to identify any significant adverse effects.

Study results demonstrated a minimal systemic absorption and a favorable safety profile for delgocitinib cream in treating adults with moderate to severe CHE. 

Specifically, the mean geometric plasma concentration of delgocitinib was 0.21 ng/mL at week 1, 0.20 ng/mL at week 4, and 0.17 ng/mL at week 16. Across all time points, the highest observed peak systemic exposure was 7.2 ng/mL, indicating that delgocitinib cream achieves only minimal systemic exposure when applied topically. This low systemic absorption contrasts with a phase 1 study where an oral dose of delgocitinib (1.5 mg) resulted in a much higher mean of 99.3 ng/mL.

Safety and tolerability results were similarly promising. Adverse events (AEs) were reported in 45.7% (43 out of 94) of patients in the delgocitinib group and 44.7% (17 out of 38) in the vehicle group. The most common AE was COVID-19 infection, reported in 11.7% of the delgocitinib group and 5.3% of the vehicle group. Only one serious adverse event occurred in the delgocitinib group (1.1%), which was determined to be unrelated to treatment. No cases of malignancy, major cardiovascular events, or venous thromboembolic events were reported, supporting a favorable safety profile.

Laboratory findings further confirmed the cream’s systemic safety. Across various laboratory markers—including hemoglobin, lymphocyte and neutrophil counts, platelet levels, alanine aminotransferase, LDL cholesterol, and triglycerides—no clinically meaningful differences were observed between the delgocitinib and vehicle groups over the 16-week study period. Minor fluctuations in these markers remained within normal ranges, with no signs of liver toxicity or impact on lipid metabolism.

References

1. Gooderham M, Thaci D, Maibach D, Melendez D, Soeholm A, Bissonnette R. Systemic exposure and safety profile of delgocitinib cream in adults with moderate to severe chronic hand eczema in the phase 3 DELTA 2 trial. Poster presented at: Elevate-Derm West Conference; November 7-10, 2024; Scottsdale, Arizona.
2. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 2) (DELTA 2). ClinicalTrials.gov identifier: NCT04872101. Updated October 17, 2024. Accessed November 8, 2024. https://clinicaltrials.gov/study/NCT04872101

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