Evaluation of Anifrolumab and Phototherapy Efficacy in Adults with Progressive Non-Segmental Vitiligo: A Randomized, Double-Blind, Phase II Study

The primary objective of this study is to evaluate the **efficacy** of the combination of anifrolumab intravenous (IV) administered every four weeks with UVB TL01 phototherapy, applied twice a week, in patients with progressive vitiligo. This will be assessed by measuring the percentage of skin repigmentation after 36 weeks of treatment using the Vitiligo Area Scoring Index (VASI) score in the experimental group receiving anifrolumab and UVB TL01. This objective is clinically relevant as it aims to determine the potential of this combination therapy to improve skin repigmentation in individuals with vitiligo, a condition characterized by the loss of skin pigmentation.

Secondary objectives include: - Evaluating the efficacy of the combination therapy using various scoring systems such as the Vitiligo European Task Force (VETF), Vitiligo Extent Score (VES), Face Vitiligo Area Scoring Index (F-VASI), Vitiligo Signs of Activity Score (VSAS), and Vitiligo Noticeability Scale (VNS). - Assessing the safety and tolerability of the combination therapy. - Evaluating the improvement in quality of life using the Dermatology Life Quality Index (DLQI), SkinDex29, and Vitiligo Impact Scale (VIPs). - Monitoring changes in blood and skin biomarkers. - Evaluating the recurrence of vitiligo 48 weeks after inclusion using various scores, including VASI, VETF, VES, F-VASI, and VSAS. - Assessing the impact on quality of life and recurrence of vitiligo using global impression and assessment scales such as the Physician’s Global Impression of Change-Vitiligo (PhGIC-V), Patient’s Global Impression of Change-Vitiligo (PaGIC-V), Total-Physician’s Global Vitiligo Assessment (T-PhGVA), and Total-Patient’s Global Vitiligo Assessment (T-PaGVA-V).

The clinical trial involves **participants** diagnosed with non-segmental (symmetrical) vitiligo, characterized by a body surface area involvement of more than 5%, excluding hands and feet. The study population includes both male and female subjects aged between 18 and 65 years, with a body weight of at least 40 kg. Participants are required to have active non-segmental vitiligo, as evidenced by new patches or the extension of old lesions within the last six months, and specific hypopigmentation characteristics under Wood's lamp examination. The trial does not include a vulnerable population. Participants must be able to provide informed consent and be affiliated with the French Social Security system. They are also required to discontinue certain medications and treatments, such as systemic steroids and topical immune modulators, prior to and during the study. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** and **tolerance** of the combination of **anifrolumab** (300 mg) administered intravenously every four weeks and phototherapy in adults with progressive non-segmental vitiligo. This is a randomized, double-blind, prospective, non-comparative proof-of-concept phase II study. The trial is expected to last for a total duration of 36 weeks, with participant involvement beginning from the screening visit and continuing through to the end-of-study visit.

Participants will undergo a sequence of study visits, starting with an inclusion (screening) visit to assess eligibility based on criteria such as age, body weight, and the extent of vitiligo. Following successful screening, participants will be randomized to receive either the active treatment or a placebo. The primary endpoint is the mean variation in the percentage of the Vitiligo Area Scoring Index (VASI) score between baseline and week 36. Secondary endpoints include safety and tolerability assessments, as well as various other vitiligo-related scoring indices measured at multiple time points throughout the study.

Study visits will occur at baseline, and at weeks 12, 24, 36, and 48, with assessments including clinical and biological exams to monitor safety and efficacy. The end-of-study visit will mark the conclusion of the participant's involvement, unless early termination is warranted. Conditions for early termination include adverse events, withdrawal of consent, or non-compliance with study protocols. Participants are expected to adhere to the study schedule and discontinue certain medications prior to and during the trial to ensure accurate assessment of the investigational treatment's effects.

The clinical trial involves the administration of **Saphnelo**, a 300 mg **concentrate for solution for infusion** containing the active substance **anifrolumab**. Anifrolumab is a protein-based therapeutic agent classified under the ATC code L04AG11. The pharmaceutical form of Saphnelo is a concentrate intended for intravenous use. The dosing regimen for this trial specifies an intravenous administration of 300 mg every four weeks. The maximum daily dose is 75 mg, with a total maximum dose of 2700 mg over the course of the 36-week treatment period. The trial aims to assess the efficacy of anifrolumab in combination with phototherapy for the treatment of progressive vitiligo.

A **placebo** is also utilized in this study as a comparator treatment. The placebo is designed to mimic the appearance and administration route of the experimental medication but does not contain any active pharmaceutical ingredients. The placebo is administered in the same manner as Saphnelo, ensuring that the study remains double-blind. This allows for an unbiased comparison of the treatment effects between the experimental group receiving anifrolumab and the control group receiving the placebo.

In addition to the experimental and placebo treatments, participants in the trial will receive standard phototherapy using UVB TL01, administered twice a week. This non-experimental treatment is part of the study's design to evaluate the combined effect of anifrolumab and phototherapy on skin repigmentation in patients with progressive vitiligo. Compliance with the dosing schedule and administration of both the experimental medication and phototherapy will be closely monitored throughout the trial to ensure adherence to the protocol and accurate assessment of treatment outcomes.

The efficacy of the clinical trial will be assessed by evaluating the combination of **anifrolumab** administered intravenously every four weeks and UVB TL01 phototherapy in adults with progressive vitiligo. The primary endpoint for efficacy evaluation is the mean variation in the percentage of the Vitiligo Area Scoring Index (VASI) score between baseline and week 36. Secondary endpoints include the mean variation in the percentage of VASI score at additional timepoints: week 12, 24, and 48. Other secondary endpoints involve the assessment of the Face Vitiligo Area Scoring Index (F-VASI), Vitiligo European Task Force (VETF) score, Vitiligo Extent Score (VES), and Vitiligo Signs of Activity Score (VSAS) at similar intervals.

Additional efficacy parameters include the Dermatology Life Quality Index (DLQI), Skindex 29, Vitiligo Impact Scale (VIPs), and vitiligo noticeability scale (VNS) scores, as well as the Physician's Global Impression of Change-Vitiligo (PhGIC-V) and Patient's Global Impression of Change-Vitiligo (PaGIC-V). The Total – Physician Global Vitiligo Assessment (T-PhGVA) and Total – Patient Global Vitiligo Assessment (T-PaGVA) will also be evaluated. Blood inflammatory markers will be measured using multiplex ELISA on patients' serum, and skin inflammatory markers will be assessed through immunofluorescence and transcriptomic analysis on skin biopsies at specified timepoints: inclusion, week 12, 24, and 36.