Phase 3 Double‑Blind Vehicle‑Controlled Trial of Topical Delgocitinib Cream in Adult Women with Lichen Sclerosus: 12‑Week Efficacy and 40‑Week Safety Evaluation

Primary objective – to establish that twice‑daily application of delgocitinib cream (8 mg/g or 20 mg/g) is superior to cream vehicle in adult female participants with Lichen Sclerosus, specifically:

• achievement of Investigator Global Assessment of LS (IGA‑LS) treatment success at Week 12;
• improvement in investigator‑rated efficacy assessments at Week 12;
• enhancement of patient‑reported efficacy outcomes at Week 12;
• reduction in Vulvar Quality of Life Index (VQLI) score from baseline to Week 12;
• sustained investigator efficacy during the long‑term continuation phase.

• long‑term efficacy of delgocitinib cream 8 mg/g and 20 mg/g;
• safety profile compared with vehicle;
• long‑term safety of both concentrations.

The trial enrolled 347 participants diagnosed with Lichen Sclerosus. Eligible individuals were adults (≥18 years) of either sex, including females of child‑bearing potential who agreed to use effective contraception and males assigned at birth without prior genital gender‑affirming surgery. Participants exhibited disease severity from mild to severe, defined by an IGA‑LS score of ≥2 at screening. Enrollment required a confirmed diagnosis based on typical clinical features and, when necessary, a supporting biopsy of the anogenital region; involvement of additional LS‑affected sites outside the anogenital area was permitted but not treated with the investigational product. Subjects needed to be capable of complying with scheduled clinic visits and trial procedures. No specific dietary or physical‑activity restrictions were stipulated. Selection adhered to the principal inclusion criteria described above.

The study is a Phase III, randomized, double‑blind, vehicle‑controlled trial evaluating twice‑daily application of delgocitinib cream (8 mg/g or 20 mg/g) versus a cream vehicle in adult participants with Lichen Sclerosus over a total of 52 weeks (a 12‑week initial treatment period followed by a 40‑week continuation period). Participants are screened for eligibility, provide informed consent, and undergo biopsy if required; eligible individuals are then randomized and receive the assigned study product at the baseline visit. Study visits are scheduled as follows:

• Screening visit – verification of inclusion criteria, baseline assessments, and biopsy if needed.
• Baseline (Day 0) – randomization, dispensing of study medication, and instruction on twice‑daily topical application.
• Follow‑up visits at Weeks 4, 8, and 12 – safety monitoring, efficacy assessments, and collection of the primary endpoint (achievement of IGA‑LS TS at Week 12).
• Continuation visits at Weeks 24, 36, and 52 – ongoing safety evaluation, efficacy reassessment, and final end‑of‑study procedures.

The investigational product consists of delgocitinib cream 8 mg/g (cream formulation). One gram of the cream is applied topically to the affected skin areas twice daily (morning and evening) for the duration of the 12‑week initial treatment period, followed by the same regimen during the 40‑week continuation phase.

A second investigational arm utilizes delgocitinib cream formulated at 20 mg/g (cream formulation). The dosing schedule mirrors that of the 8 mg/g arm: 1 g applied topically twice daily throughout both the initial 12‑week period and the subsequent 40‑week continuation period.

The control arm receives a cream vehicle identical in appearance, texture, and packaging to the active creams but containing no active pharmaceutical ingredient. Participants apply 1 g of the vehicle topically twice daily on the same schedule as the active arms.

All study medications are dispensed in pre‑measured tubes. Participants are instructed to record each application in a study diary, and compliance is assessed by counting returned tubes and reviewing diary entries at each study visit.

Efficacy assessment focuses on achieving the Investigator Global Assessment of Lichen Sclerosus Treatment Success (IGA-LS TS) at Week 12 as the primary endpoint. Participants are evaluated at baseline and at scheduled visits during the initial 12‑week treatment period, with the primary comparison made between delgocitinib cream (8 mg/g or 20 mg/g) and the vehicle cream.

Secondary efficacy parameters include: achievement of IGA‑LS TS at Week 8; change from baseline in the Clinical Lichen Sclerosus Severity Score (CLISSCO) at Weeks 12 and 52; reduction of weekly average skin pain numeric rating scale (skin pain NRS) by ≥4 points at Weeks 8, 12, and 52 in participants with baseline scores ≥4; reduction of weekly average itch NRS by ≥4 points at the same time points; change in the Vulvar Quality of Life Index (VQLI) from baseline to Week 12; IGA‑LS TS status at Week 52, including achievement of an IGA‑LS score of 0 or 1 among those who met TS at Week 12; time to IGA‑LS TS from baseline to Week 52 and time to IGA‑LS ≥2 from Week 12 to Week 52; and maintenance of CLISSCO architectural changes domain score without increase at Week 52. Safety‑related secondary measures (treatment‑emergent adverse events) are also recorded from baseline to Week 12 and from Week 12 to Week 54.

Assessments are conducted using validated investigator‑rated scales (IGA‑LS TS, CLISSCO) and patient‑reported outcome instruments (skin pain NRS, itch NRS, VQLI). Data collection occurs at baseline and at the specified weekly or monthly visits (Weeks 8, 12, 52, and up to Week 54), with statistical analysis planned to compare the proportion of participants achieving each dichotomous endpoint and the mean change in continuous scores between active and vehicle groups.