B7981080 - A PHASE 3 RANDOMIZED, DOUBLE-BLIND, 52-WEEK PLACEBOCONTROLLED MULTI-CENTER STUDY WITH A DOUBLE-BLIND 52-WEEK EXTENSION PERIOD WITH RANDOMIZED DOSE UP/DOSE DOWN TITRATION INVESTIGATING THE EFFICACY, SAFETY, AND TOLERABILITY OF RITLECITINIB IN ADULT PARTICIPANTS WITH NONSEGMENTAL VITILIGO

The primary objective of this study is to assess the **efficacy** of ritlecitinib 100 mg once daily (QD) compared to placebo in adult participants with nonsegmental vitiligo. This objective is clinically relevant as it aims to determine the potential therapeutic benefit of ritlecitinib in managing this chronic skin condition, which is characterized by depigmented patches and can significantly impact the quality of life.

Secondary objectives include:

• Part Ia: Comparing the efficacy of ritlecitinib 100 mg QD versus placebo on T-VASI50, Patient Global Impression of Change – Face (PGIC-F), Patient Global Impression of Change – Overall Vitiligo (PGIC-V), PGIS-F, PGIS-V, and F-VASI75 at various time points in participants with nonsegmental vitiligo.
• Part Ia: Evaluating the efficacy of ritlecitinib 100 mg QD versus placebo, ritlecitinib 50 mg QD versus placebo, and ritlecitinib 100 mg QD versus ritlecitinib 50 mg QD as measured by other clinical outcome assessments and patient-reported outcomes (PROs) over time.
• Part Ib: Evaluating the efficacy of ritlecitinib 100 mg QD, ritlecitinib 50 mg QD, and placebo over time as measured by other clinical outcomes and PROs in participants previously treated for 52 weeks with these regimens.
• Part II: Evaluating the efficacy of ritlecitinib 100 mg QD over time in adult participants with nonsegmental vitiligo, as well as its efficacy as measured by PROs.
• Part Ib: Assessing response based on F-VASI100 at all time points in the schedule of activities (SoA).

The clinical trial involves a total of **1,095 participants** diagnosed with **nonsegmental vitiligo**. The study population includes both male and female subjects, aged **18 years and older**, with a clinical diagnosis of nonsegmental vitiligo for at least three months. Participants were selected based on specific criteria, including body surface area involvement between 4% and 60%, excluding certain areas such as the palms and soles. The trial includes individuals with either active or stable nonsegmental vitiligo. The study population is characterized by a diverse age range and includes a vulnerable population. Lifestyle factors such as diet and physical activity were not specified by the sponsor. The trial aims to evaluate the efficacy, safety, and tolerability of ritlecitinib in this population.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of **ritlecitinib** in adult participants with **nonsegmental vitiligo**. The trial consists of a 52-week placebo-controlled period followed by a 52-week double-blind extension period with randomized dose up/dose down titration. The primary objective is to compare the efficacy of ritlecitinib 100 mg once daily versus placebo, and to assess the long-term safety and tolerability of ritlecitinib 100 mg and 50 mg once daily. The trial is expected to conclude by July 2027, with recruitment starting in May 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years) and a clinical diagnosis of nonsegmental vitiligo for at least three months. The screening will also assess body surface area involvement and vitiligo activity. Following the screening, participants will be randomized to receive either ritlecitinib or placebo. Follow-up visits will occur at regular intervals to monitor treatment response and safety, with assessments including the Facial Vitiligo Area Scoring Index (F-VASI) and Total Vitiligo Area Scoring Index (T-VASI). The end-of-study visit will evaluate the overall outcomes and any adverse events experienced during the trial.

The expected length of participant involvement is up to 104 weeks, encompassing both the initial and extension periods. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, clinically significant laboratory abnormalities, or withdrawal of consent by the participant. The trial's design ensures rigorous monitoring and evaluation to maintain participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **Ritlecitinib Tosilate**, an investigational medication, in adult participants with nonsegmental vitiligo. Ritlecitinib Tosilate is provided in the form of a hard capsule and is administered orally. The maximum daily dose is 100 mg, with a total maximum dose of 36,400 mg over a treatment period of up to 52 weeks. The active substance, Ritlecitinib Tosilate, is a small organic molecule of chemical origin. The trial includes a dose up/dose down titration to evaluate the efficacy, safety, and tolerability of the medication.

**Dexamethasone** is used as a non-experimental treatment in the study. It is administered in tablet form, also via the oral route. The maximum daily dose of Dexamethasone is 4 mg, with a total maximum dose of 96 mg over a 12-week period. Dexamethasone serves as a standard-of-care therapy to assess its comparative effects alongside the investigational medication.

The study also includes a **placebo** for PF-06651600-15, available in 50 mg and 100 mg dosages. The placebo is composed of inactive ingredients with no pharmacological activity and is used to maintain the double-blind nature of the trial. The placebo is administered orally, mirroring the administration route of the investigational medication, to ensure consistency in the study design.

The efficacy of the clinical trial investigating **Ritlecitinib** in adult participants with nonsegmental vitiligo will be assessed using several primary and secondary endpoints. The primary efficacy endpoint for Part Ia of the trial 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 T-VASI50 at Weeks 24, 36, and 52, and the response based on PGIC-F, which is defined as at least "moderately better" reported change in the severity of vitiligo on the face from baseline at Weeks 36 and 52.

Additional secondary endpoints involve the response based on PGIC-V, indicating a "moderately better" change in total body vitiligo from baseline at Weeks 36 and 52, and the response based on improvement in PGIS-F and PGIS-V at Weeks 36 and 52. The trial will also measure the percent change from baseline in F-VASI and T-VASI at all time points in the Schedule of Activities (SoA). The efficacy assessments will be conducted at specified time points throughout the trial, including Weeks 24, 36, and 52, using validated scales and patient-reported outcomes to ensure accurate and reliable data collection and analysis.