B7981040 - A PHASE 3 RANDOMIZED, DOUBLE-BLIND, 52-WEEK PLACEBOCONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY, SAFETY, AND TOLERABILITY OF RITLECITINIB IN ADULT AND ADOLESCENT PARTICIPANTS WITH NONSEGMENTAL VITILIGO

The primary objective of this study is to compare the **efficacy** of ritlecitinib 50 mg once daily (QD) versus placebo in participants with nonsegmental vitiligo. Additionally, the study aims to evaluate the safety and tolerability of ritlecitinib over time in this patient population. This is clinically relevant as nonsegmental vitiligo is a chronic skin condition characterized by depigmented patches, and effective treatment options are limited. Understanding the efficacy and safety of ritlecitinib could provide a new therapeutic option for managing this condition.

Secondary objectives include:

• Comparing the efficacy of ritlecitinib 50 mg QD versus placebo on F-VASI75 at Weeks 24 and 36.
• Comparing the efficacy on T-VASI50 at Weeks 24, 36, and 52.
• Comparing the efficacy on percentage change from baseline (% CFB) in F-VASI at Weeks 24, 36, and 52.
• Comparing the efficacy on % CFB in T-VASI at Weeks 24, 36, and 52.
• Comparing the efficacy on PGIS-F at Weeks 24, 36, and 52.
• Comparing the efficacy on PGIS-V at Weeks 24, 36, and 52.

These secondary objectives aim to provide a comprehensive assessment of the treatment's impact on various clinical endpoints, further elucidating its potential benefits in treating nonsegmental vitiligo.

The clinical trial involves a total of **519 participants** diagnosed with **nonsegmental vitiligo**. The study population includes both male and female subjects, with an age range starting from 12 years, contingent upon local IRB/EC and regulatory health authority approval, and extending to adults aged 18 years and older. Participants were selected based on specific criteria, including a clinical diagnosis of nonsegmental vitiligo for at least three months and a body surface area (BSA) involvement of 4%-60%, excluding certain areas such as the palms and soles. The trial also requires a minimum BSA involvement of 0.5% on the face. Participants must have either active or stable nonsegmental vitiligo at both screening and baseline visits. All other treatments for vitiligo must be discontinued from screening through the final follow-up visit. The trial includes a vulnerable population, ensuring comprehensive safety and efficacy evaluations of the investigational treatment.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of **Ritlecitinib tosilate** in adult and adolescent participants with nonsegmental vitiligo. The trial is set to last for 52 weeks, with an estimated recruitment start date of March 25, 2023, and an estimated end date of June 3, 2024. Participants will be randomly assigned to receive either Ritlecitinib tosilate, a placebo, or **Dexamethasone** as an auxiliary treatment. The primary objective is to compare the efficacy of Ritlecitinib 50 mg once daily versus placebo, while also evaluating the safety and tolerability of the treatment over time.

The study involves several key visits, beginning with a screening visit to confirm eligibility based on criteria such as age, clinical diagnosis of nonsegmental vitiligo, and body surface area involvement. Participants must agree to discontinue all other treatments for vitiligo from the screening through the final follow-up visit. Following the screening, participants will attend baseline visits to establish initial measurements and begin the treatment regimen. Follow-up visits will occur at regular intervals to monitor progress, assess response based on F-VASI75 and T-VASI50, and evaluate any treatment-emergent adverse events or clinically significant laboratory abnormalities. The end-of-study visit will conclude the trial, with final assessments of efficacy and safety outcomes.

Participant involvement is expected to last the full 52 weeks of the trial, barring any conditions that may necessitate early termination, such as the occurrence of serious adverse events or significant non-compliance with the study protocol. The primary endpoints include achieving at least a 75% improvement in F-VASI from baseline at Week 52 and monitoring the incidence of adverse events. Secondary endpoints will assess responses at Weeks 24, 36, and 52, including improvements in F-VASI, T-VASI, and patient-reported outcomes. The trial is conducted under strict regulatory oversight to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Ritlecitinib tosilate**, an investigational medication, in the form of a hard capsule. The active substance, ritlecitinib tosilate, is a small molecule with a chemical origin. Participants will receive a daily oral dose of 50 mg, with the treatment period extending up to 52 weeks. The medication is provided by Pfizer Inc. and is identified by the sponsor product code PF-06651600. The trial aims to evaluate the efficacy, safety, and tolerability of ritlecitinib in individuals with nonsegmental vitiligo.

**Dexamethasone** is included as an auxiliary treatment in the study. It is administered in tablet form, with a maximum daily dose of 4 mg and a total maximum dose of 96 mg over a 12-week period. The active substance, dexamethasone, is also of chemical origin. The route of administration is oral, and it serves as a standard-of-care therapy to support the primary investigational treatment.

A **placebo** is utilized in the trial to serve as a comparator to the investigational medication, Ritlecitinib tosilate. The placebo is designed to match the 50 mg dosage of the investigational drug and is administered orally. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias and enhancing the reliability of the study outcomes.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the response based on **F-VASI75**, defined as at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI) from baseline at Week 52. Secondary endpoints include the response based on F-VASI75 at Weeks 24 and 36, response based on T-VASI50 at Weeks 24, 36, and 52, and percentage change from baseline (% CFB) in F-VASI and T-VASI at Weeks 24, 36, and 52. Additionally, improvements in Patient Global Impression of Severity for Face (PGIS-Fb) and Patient Global Impression of Severity for Vitiligo (PGIS-Vc) at Weeks 24, 36, and 52 will be evaluated.

The efficacy parameters will be measured and collected at specified timepoints throughout the trial, including Weeks 24, 36, and 52. The assessments will utilize validated scales such as the F-VASI and T-VASI, which are commonly used in clinical trials for nonsegmental vitiligo. The analysis will focus on the comparison of ritlecitinib 50 mg QD versus placebo in achieving the defined endpoints. The trial is designed to provide a comprehensive evaluation of the efficacy of ritlecitinib in adult and adolescent participants with nonsegmental vitiligo over a 52-week period.