Phase 3 Randomized, Double‑Blind, Placebo‑Controlled Study of Dupilumab in Adults with Moderate‑to‑Severe Lichen Simplex Chronicus (Neurodermatitis)

The primary objective of this study is to demonstrate the **efficacy** of dupilumab in treating pruritus associated with Lichen Simplex Chronicus (LSC) in adult participants who have moderate-to-severe LSC that is inadequately controlled by topical therapies. This is clinically relevant as pruritus significantly impacts the quality of life in patients with LSC, and effective management is crucial for improving patient outcomes.

Secondary objectives include:

• To demonstrate the efficacy of dupilumab on additional pruritus endpoints in LSC.
• To demonstrate the efficacy of dupilumab in decreasing itch-related sleep disturbance.
• To demonstrate improvement in health-related quality of life (HRQoL).
• To evaluate the immunogenicity of dupilumab.
• To evaluate safety outcome measures.

The clinical trial involves a total of **124 participants** diagnosed with **neurodermatitis**, specifically focusing on those with moderate-to-severe lichen simplex chronicus (LSC) inadequately controlled by topical therapies. The study population includes both male and female adults, aged 18 years and older, who have a history of LSC for at least six months prior to the screening visit. Participants were selected based on specific criteria, including an Investigator’s Global Assessment (IGA) score of 3 or higher, and a history of failing a 2-week course of medium-to-superpotent topical corticosteroid with or without topical calcineurin inhibitor treatment. The trial also considers lifestyle factors such as the use of appropriate contraceptive measures. The population includes individuals from a vulnerable group, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographics.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of **dupilumab** for the treatment of pruritus associated with **Lichen Simplex Chronicus** (LSC) in adults. The trial aims to demonstrate the efficacy of dupilumab in adult participants with moderate-to-severe LSC that is inadequately controlled by topical therapies. The study will involve the administration of dupilumab as a solution for injection in pre-filled syringes, with a maximum daily dose of 300 mg and a total dose not exceeding 3900 mg over a 24-week treatment period.

Participants will be randomly assigned to receive either dupilumab or a matched placebo. The trial will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, severity of LSC, and history of treatment failure with topical corticosteroids. The screening period may last up to 28 days. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety, with assessments including the Worst-Itch Numerical Rating Scale (WI-NRS) and other quality of life measures. The primary endpoint is the proportion of participants achieving a reduction in the weekly average of daily WI-NRS by at least 4 points from baseline to Week 24.

Secondary endpoints include changes in WI-NRS, itch-related sleep disturbance, and quality of life scores from baseline to Week 24, as well as the incidence of treatment-emergent adverse events. The trial is expected to conclude with an end-of-study visit at Week 24, where final assessments will be conducted. Participant involvement is anticipated to last approximately 24 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The estimated recruitment start date is January 10, 2025, with the trial expected to end by July 5, 2027.

The clinical trial involves the use of **Dupilumab**, an experimental medication, for the treatment of pruritus associated with **Lichen Simplex Chronicus** in adults. **Dupilumab** is administered as a **solution for injection in a pre-filled syringe**. The active substance, **dupilumab**, is a protein of other origin, developed by Sanofi Aventis Recherche et Développement (SAR). The maximum daily dose of **Dupilumab** is 300 mg, with a total maximum dose of 3900 mg over a treatment period of 24 weeks. The route of administration is via injection, and the dosing schedule is determined by the study protocol to ensure optimal efficacy and safety. Participant compliance with the dosing regimen is monitored throughout the trial to maintain the integrity of the study data.

The study also includes a **matched placebo** for the test product, which serves as a comparator treatment in this double-blind, placebo-controlled trial. The placebo is designed to match the experimental medication in appearance and administration method, ensuring that neither the participants nor the investigators can distinguish between the active treatment and the placebo. This approach is critical for maintaining the study's blinding and reducing bias in the assessment of **Dupilumab's** efficacy and safety. The placebo does not contain any active substance and is used to evaluate the true effect of the experimental medication against a control.

The efficacy of **dupilumab** in the treatment of pruritus associated with Lichen Simplex Chronicus (LSC) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants who achieve an improvement, defined as a reduction of 4 or more points, in the weekly average of daily Worst-Itch Numerical Rating Scale (WI-NRS) scores from baseline to Week 24. Secondary endpoints include changes in the weekly average of daily WI-NRS scores, Itch-related Sleep Disturbance NRS, ItchyQoL scores, and Dermatology Life Quality Index (DLQI) total scores from baseline to Week 24. Additionally, the proportion of participants with a reduction of 4 or more points in the weekly average of daily WI-NRS scores by Week 12 will be evaluated. The incidence of treatment-emergent anti-drug antibodies (ADA) against dupilumab and the percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) will also be monitored.

These efficacy parameters will be measured at specified timepoints, including baseline, Week 12, and Week 24, using validated scales and patient-reported outcomes. The data collection will involve the use of numerical rating scales for itch severity and sleep disturbance, as well as quality of life assessments specific to dermatological conditions. The analysis will focus on comparing the changes from baseline in these scores to determine the therapeutic impact of dupilumab on LSC-related pruritus.