Efficacy of Deucravacitinib in Patients with Lichen Planus: A Multicenter, Phase II, Proof-of-Concept Study

The primary objective of this study is the evaluation of the **efficacy** of deucravacitinib on objective clinical symptoms and disease activity in patients with **lichen planus**. This is clinically relevant as it aims to determine the therapeutic potential of deucravacitinib, a selective TYK2 inhibitor, in managing the symptoms and progression of lichen planus, a chronic inflammatory condition.

Secondary objectives include:

• Assessing whether the administration of deucravacitinib is associated with reduced inflammatory parameters through mRNA-based gene expression analysis of IFN genes (e.g., CXCL10, CXCL9, CCL5, MxA, BLyS, TRAIL).
• Evaluating the improvement in quality of life using the Dermatological Quality of Life Index (DLQI), a validated score.
• Determining the improvement of itching via the Numeric Rating Scale (NRS) for average itch during the past 24 hours.
• Assessing the improvement or reduction in the amount of steroids used by patients.

The clinical trial focuses on evaluating the efficacy of **deucravacitinib** in patients with **lichen planus**. The study population includes both male and female participants aged 18 years and older. Participants are required to have histologically proven and symptomatic lichen planus, with a LiPADI Activity Score of 6 or higher, or 3 or higher for those with mucosal involvement only. The trial does not involve a vulnerable population. Participants must be capable of following study instructions and willing to attend all required visits. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a multicenter, phase II study designed to evaluate the efficacy of **deucravacitinib**, a selective TYK2 inhibitor, in patients with **lichen planus**. The trial employs a randomized, double-blind, placebo-controlled design to ensure the reliability and validity of the results. Participants will be randomly assigned to receive either deucravacitinib or a placebo, with neither the participants nor the investigators aware of the group assignments, thus maintaining the double-blind nature of the study. The trial is expected to last until December 2025, with participant recruitment starting in November 2023.

The study involves a series of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), a histologically proven diagnosis of lichen planus, and a LiPADI Activity Score of ≥6 or ≥3 for those with mucosal involvement only. Participants must provide written informed consent and demonstrate the ability to comply with study instructions and visit schedules. Following the screening, participants will attend multiple follow-up visits, including baseline (V1, day 1), interim assessments (V3, V4/OLE-V1, SC-1, SC-2, OLE-V2, SC-3, OLE-V3), and an end-of-study (EOS) visit (V4, day 112). These visits are designed to monitor changes in clinical symptoms, gene expression profiles, and quality of life measures such as the DLQI and Itch NRS scores.

Participant involvement is expected to last up to 339 days, with the possibility of early termination if specific conditions arise, such as adverse events, non-compliance with the study protocol, or withdrawal of consent. The primary endpoint is the change in objective clinical symptoms, measured by the LiPADI Activity Score from baseline to the EOS visit. Secondary endpoints include changes in gene expression profiles and quality of life measures, as well as the amount of steroids used. The trial aims to provide valuable insights into the therapeutic potential of deucravacitinib for lichen planus, contributing to the development of effective treatment strategies for this condition.

The clinical trial involves the administration of **deucravacitinib**, a stable deuterium-containing, highly selective small molecule inhibitor for Tyk2. The pharmaceutical form of deucravacitinib is a film-coated tablet, and it is administered orally. The dosage is set at 6 mg per day, with a maximum total dose amounting to 2034 mg over the course of the treatment period. The maximum treatment period is 339 days. The active substance in deucravacitinib is chemically derived, and the product is identified by the sponsor product code BMS-986165. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** designed to match deucravacitinib 6 mg, manufactured by Bristol-Myers Squibb (BMS). The placebo is a film-coated tablet, formulated as an age-appropriate oral solid dosage form. The ingredients of the placebo include lactose monohydrate, microcrystalline cellulose, magnesium stearate, and Opadry II coating. The placebo is administered orally, following the same dosing schedule as the experimental medication, to ensure blinding and maintain the integrity of the trial. Compliance with the administration of the placebo will be monitored in a manner consistent with the experimental treatment.

The efficacy of deucravacitinib in the treatment of **Lichen Planus** will be assessed through a multicenter, phase II clinical trial. The primary endpoint for evaluating efficacy is the change in objective clinical symptoms, as measured by the Lichen Planus Activity and Damage Index (LiPADI) Activity Score, from baseline (V1, day 1) to the end of the study (EOS, V4, day 112). Secondary endpoints include changes in the LiPADI Activity Score at various timepoints (V3, V4/OLE-V1, SC-1, SC-2, OLE-V2, SC-3, and OLE-V3) in both treatment arms, as well as differences in the IFN gene expression profile (including CXCL10, CXCL9, CCL5, MxA, BLyS, TRAIL) in peripheral blood and skin or lesional oral mucosa between the placebo and treatment arms. Additional secondary endpoints involve changes in the Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS) from baseline to EOS and other specified timepoints, as well as the change in the amount of steroids used from baseline to EOS between the placebo and treatment arms.