Open-Label Pilot Study Evaluating Safety and Tolerability of Topical Delgocitinib Cream in Patients with Cutaneous T‑Cell Lymphoma (Mycosis Fungoides)

The primary objective of this open‑label, proof‑of‑concept pilot study is to assess the safety and tolerability of a topical Janus kinase (JAK) inhibitor (delgocitinib 20 mg/g cream) in patients with cutaneous T‑cell lymphoma. Evaluation of adverse event frequency, severity, and relatedness will define the risk‑benefit profile of this novel local therapy and determine its suitability for further clinical development.

The trial enrolled adult men and women, all aged 18 years or older, who had a histologically confirmed diagnosis of mycosis fungoides (stage IA, IB, or IIA) within the spectrum of Cutaneous T-cell lymphoma and exhibited stable disease requiring palliative therapy. Participants were required to have maintained a consistent medication regimen for at least two months prior to enrollment and to be capable of providing informed consent. No specific dietary or physical‑activity restrictions were imposed, and usual lifestyle habits were permitted. The sponsor did not provide the total number of participants enrolled. The study population was selected on the basis of these inclusion criteria, and both sexes were represented. The primary aim was to assess the safety and tolerability of topical JAK inhibitors in this patient cohort.

The investigation is an open‑label, phase 4, proof‑of‑concept pilot study evaluating the safety, tolerability, and skin‑response effects of a topical JAK inhibitor (delgocitinib 2 mg/g cream) in adults with histologically confirmed Cutaneous T‑cell lymphoma (mycosis fungoides, stages IA–IIA) and stable disease. After a screening visit to verify eligibility and obtain informed consent, participants receive the study medication applied twice daily for 16 weeks. Follow‑up visits are scheduled at weeks 4, 8, 12, and 16 to perform safety assessments, record adverse events, and evaluate efficacy using the modified Severity‑Weighted Assessment Tool (mSWAT), patient‑reported pruritus (Numeric Rating Scale), and skin‑related quality of life (Skindex‑29); skin biopsies and transepidermal water loss measurements are obtained for mechanistic analyses. The end‑of‑study visit at week 16 includes final efficacy and safety evaluations and collection of post‑treatment specimens. Participant involvement therefore spans approximately 18 weeks, including the screening period. Early termination may occur if a participant experiences a serious adverse event, unacceptable toxicity, disease progression, withdraws consent, or violates major protocol requirements.

The investigational product is Anzupgo 20 mg/g cream, a topical formulation containing the active substance delgocitinib. Each gram of cream delivers 20 mg of delgocitinib, corresponding to a concentration of 2 mg/g. The cream is applied to the affected skin area according to the investigator‑specified regimen and is administered via topical use.

No placebo, standard‑of‑care therapy, or other comparator treatment is incorporated into the study protocol.

Efficacy will be evaluated primarily by assessing skin response through the change in modified Severity-Weighted Assessment Tool (mSWAT) score from baseline to the end of treatment at Week 16. The overall skin response category (complete response, partial response, stable disease, or progressive disease) will be assigned according to predefined mSWAT‑based response criteria, and the overall response rate will be calculated as the proportion of subjects achieving a complete or partial response.

Secondary efficacy assessments include the change from baseline in patient‑reported pruritus using a Numeric Rating Scale (NRS), and the change in skin‑related quality of life measured by the Skindex‑29 questionnaire. Mechanistic effects of the topical JAK inhibitor will be explored by performing digital spatial and transcriptomic profiling on lesional and non‑lesional skin biopsies, together with transepidermal water loss (TEWL) analysis to detect alterations in the skin barrier. All efficacy parameters will be collected at baseline and at the Week 16 end‑of‑treatment visit, and data will be analyzed using appropriate statistical methods to compare baseline and post‑treatment values.