A Multicenter, Evaluator-Blinded Study Comparing Ritlecitinib and Narrowband UVB Combination Therapy Versus Ritlecitinib Monotherapy in Vitiligo Patients

The primary objective of this study is to compare the mean percentage change of **F-VASI** (Facial Vitiligo Area Scoring Index) and **T-VASI** (Total Vitiligo Area Scoring Index) between the baseline and week 52 in patients with vitiligo. This is clinically relevant as it evaluates the efficacy of the combination therapy of ritlecitinib and nbUVB compared to ritlecitinib monotherapy, potentially offering a more effective treatment option for vitiligo, a condition characterized by depigmented skin patches.

Secondary objectives include:

• Comparing the proportion of patients achieving F-VASI-50, F-VASI-75, and F-VASI-90 at various time points (week 24, 36, 52, and 72).
• Comparing the proportion of patients achieving T-VASI50 and T-VASI75 at specified weeks.
• Evaluating the mean percentage change from baseline in F-VASI and T-VASI at weeks 12, 24, 36, and 72.
• Assessing changes in the Vitiligo Noticeability Scale (VNS) and quality of life using the VIPs short form.
• Evaluating the safety and tolerability of the combination therapy.
• Comparing the evolution of patient global impression and disease activity and stabilization between baseline and subsequent visits.

The clinical trial involves **participants** diagnosed with non-segmental **vitiligo**, a condition characterized by the loss of skin pigmentation. The study population includes both men and women aged 18 years and older. Participants are required to have a body surface area (BSA) involvement between 4% and 60%, excluding the palms, soles, and dorsal aspect of the feet, with at least 0.5% involvement on the face. The trial does not include a vulnerable population. Participants must have active and stable vitiligo, with specific F-VASI and T-VASI scores. Women of childbearing potential are required to use effective contraception and have a negative pregnancy test at baseline. The total number of participants is not provided by the sponsor. Participants must be affiliated with a social security system and have signed informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **ritlecitinib** in combination with narrowband ultraviolet B (nbUVB) therapy compared to ritlecitinib alone for the treatment of **vitiligo**. This is a prospective, multicentric, evaluator-blinded, interventional study. The trial employs a randomized, controlled design to ensure the reliability of the results. Participants will be randomly assigned to one of the treatment groups, and both the participants and the evaluators will be blinded to the treatment allocation to minimize bias. The trial is expected to commence recruitment in September 2025 and conclude by November 2028, with a total duration of approximately 72 weeks for each participant.

The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility criteria will be assessed, including age, extent of body surface area (BSA) involvement, and stability of vitiligo. Participants must have non-segmental vitiligo, be 18 years or older, and meet specific BSA involvement criteria. Women of childbearing potential must use effective contraception and have a negative pregnancy test at baseline. Following successful screening, participants will be enrolled and randomized into the study.

Follow-up visits will occur at regular intervals to monitor the progress of the treatment and assess primary and secondary endpoints. The primary endpoint is the mean percentage change in the Facial Vitiligo Area Scoring Index (F-VASI) and Total Vitiligo Area Scoring Index (T-VASI) from baseline to week 52. Secondary endpoints include various measures of vitiligo improvement, quality of life assessments, and the recording of any adverse events. The end-of-study visit will involve a final assessment of the treatment outcomes and the collection of any remaining data.

Participant involvement is expected to last for the full 72-week duration unless early termination is warranted. Conditions that may lead to early termination include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the study period.

The clinical trial involves the use of **Litfulo 50 mg hard capsules** as the experimental medication. The active substance in these capsules is **ritlecitinib**, a chemical compound. The pharmaceutical form of the medication is a hard capsule, and it is administered orally. The dosage is set at 50 mg per capsule, with a maximum daily dose of 100 mg. The total maximum dose over the treatment period is 504 grams. The treatment duration is up to 72 weeks. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the efficacy of ritlecitinib in treating **vitiligo**.

In addition to the experimental treatment, the study includes a comparator treatment involving a combination approach with ritlecitinib and narrowband ultraviolet B (nbUVB) therapy. This combination is compared to the administration of ritlecitinib alone. The study is designed as a prospective multicentric evaluator-blinded interventional study. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The main objective is to compare the mean percentage change of F-VASI and T-VASI between the baseline and week 52.

Efficacy in this clinical trial will be assessed by evaluating the mean percentage change in the **Facial Vitiligo Area Scoring Index (F-VASI)** and the Total Vitiligo Area Scoring Index (T-VASI) from baseline to week 52. The primary endpoint involves calculating the percentage change from baseline (%CFB) in F-VASI at week 52, defined as %CFB FVASIW0-W52 = (FVASIw0 - FVASIw52)/FVASIw0. Secondary endpoints include achieving F-VASI reductions of 50%, 75%, and 90% at various timepoints, with F-VASI 90 being assessed at weeks 24, 36, 52, and 72. T-VASI reductions of 50% and 75% will also be evaluated at specified intervals.

Additional efficacy assessments will include the Vitiligo Noticeability Scale (VNS) as a patient-reported outcome, comparing the patient's current state to baseline photographs. Quality of life will be measured using the Vitiligo Impact Patient Scale (VIPs) short form at baseline, week 36, week 52, and week 72. The activity of the disease will be assessed using the Vitiligo Scoring Activity Score (VSAS) at multiple timepoints, and response based on disease stabilization will be defined as a less than 15-point increase in T-VASI score between baseline and subsequent visits. Patient global impressions after treatment will be measured using PGIC (F/V) and PGIS (F/V) at each visit. All adverse events, both clinical and biological, will be documented throughout the study period, noting their type, grade, and severity.