DELTA 3 Showcases Long-Term Safety and Efficacy of Delgocitinib for Chronic Hand Eczema

Image Credit: © ReaLiia - stock.adobe.com

Results of LEO Pharma’s DELTA 3 trial have confirmed the long-term safety and efficacy of delgocitinib cream (20 mg/g) on chronic hand eczema (CHE) for up to 52 weeks.¹ Disease control was maintained or improved with noticeable reductions in pain and itch.

Background

There are currently no topical treatments that have been specifically developed for moderate to severe CHE.² Oral alitretinoin is currently the only approved therapy. Delgocitinib is a first-in-class topical JAK inhibitor that blocks pro-inflammatory pathways. In the previous double-blind DELTA 1 and 2 parent studies, delgocitinib cream 20 mg/g was well tolerated over 16 weeks of treatment.³ When compared to placebo, greater improvements in efficacy were seen. 

Methods and Materials

The DELTA 3 phase 3, open-label extension trial (NCT04949841) was conducted at 99 centers in 10 countries (Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, and the United Kingdom) from August 2021 to September 2023. This involved a 4-week screening, a 36-week treatment period, and a 2-week safety follow-up.

The study included 801 adult patients who were previously treated for 16 weeks in either the DELTA 1 or DELTA 2 study and still had an Investigator's Global Assessment for CHE (IGA-CHE) score of ≥2 at baseline. Participants were treated twice daily (every 12 hours) on an as-needed basis for 36 additional weeks. Treatment was stopped once an IGA-CHE score of ≤1 (clear or almost clear) was reached.

Investigators observed any treatment-emergent adverse effects as a primary endpoint. As secondary endpoints, IGA-CHE scores of 0/1 and a ≥75% or ≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores were utilized to determine treatment response.

“The IGA-CHE instrument, as a single item measure of CHE severity, is a strong, valid, and reliable measure of CHE severity and corresponding clinically meaningful changes, supporting its use as an endpoint in CHE clinical trials and clinical practice,” the authors wrote.

Results

Delgocitinib was overall well-tolerated, with any stinging, burning, and tolerability issues improving from week 1 (83.9%) to week 36 (90.2%). There was also no increase in the rate of adverse effects compared to DELTA 1 and 2. The most reported ones were COVID-19 infections (16.7%), nasopharyngitis (16.0%), and upper respiratory tract infections (4.0%). The majority of adverse events were mild or moderate (78.9%) and the few serious adverse effects that occurred were not related to the drug.

Patients previously treated with delgocitinib in DELTA 1 and 2 maintained their disease control while those who were treated previously with placebo saw large improvements, especially in itch and pain. Almost half of patients previously treated with delgocitinib achieved IGA-CHE 0/1 during the 36-week treatment. Similarly, 54.4% of those previously treated with the placebo reached the same.

The proportion of patients achieving HECSI-75 and HECSI-90 responses was maintained in both groups, with an increase over time in the patients who initially took placebo. Mean HECSI and HESD scores decreased within the first 16 weeks and then remained stable until the trial conclusion.

Several patients re-initiated therapy following an off-treatment period. The median estimated time to achieve IGA-CHE 0/1 again was 8 weeks. Over 80% of patients regained their IGA-CHE 0/1 score at the end of the trial (95% CI: 72.5%-87.7%).

Most of the participants were white (91.4%), which limits the generalization of these findings for other ethnicities. Additionally, the open-label trial design could be considered a limitation, so the researchers recommend real-world evidence to further confirm delgocitinib’s long-term safety in clinical practice.

Conclusion

Overall, long-term delgocitinib use of up to a year was well-tolerated, safe, and effective in adult patients with moderate to severe CHE. Patients who continued delgocitinib from the previous DELTA trials maintained their disease clearance while patients who were previously treated with placebo cream saw improvement. Additionally, those who stopped treatment after disease remission were still able to regain a response once the therapy was restarted.

References 

1. Gooderham M, Molin S, Bissonnette R, et al. Long-term safety and efficacy of delgocitinib cream for up to 52 weeks in adults with Chronic Hand Eczema: results of the phase 3 open-label extension DELTA 3 trial following the DELTA 1 and 2 trials. J Am Acad Dermatol. Published online March 11, 2025. doi:10.1016/j.jaad.2025.03.008

2. Lee GR, Maarouf M, Hendricks AK, Lee DE , Shi VY. Current and emerging therapies forhand eczema. Dermatol Ther 2019;32:e12840.

3. Bissonnette R, Warren R, Pinter A, Agner T, Gooderham G, Schuttelaar M et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials. The Lancet 2024.