Phase 3 Randomized Withdrawal and Dose-Up Titration Study of Ritlecitinib Tosilate in Adult and Adolescent Patients with Nonsegmental Vitiligo

The primary objective of this study is to evaluate the long-term **safety** and tolerability of ritlecitinib 100 mg QD and ritlecitinib 50 mg QD in adult and adolescent participants with nonsegmental vitiligo. This is clinically relevant as it aims to ensure that the treatment is safe for long-term use in managing this chronic skin condition, which can significantly impact patients' quality of life.

Secondary objectives include:

• Evaluating the efficacy of ritlecitinib 100 mg QD and 50 mg QD over time as measured by clinical outcomes in adult and adolescent participants who were previously treated for 52 weeks with ritlecitinib 50 mg or placebo in Study B7981040.
• Assessing the efficacy of ritlecitinib 100 mg QD and 50 mg QD over time as measured by patient-reported outcomes (PROs) in the same population.

The clinical trial involves a total of **331 participants** diagnosed with **nonsegmental vitiligo**. The study population includes both male and female subjects, with an age range encompassing adolescents aged 12 to less than 18 years and adults aged 18 years and older. Participants were selected based on their completion of a prior study (Study B7981040) and their agreement to refrain from using other treatments for vitiligo during the trial period. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Participants are required to have completed 52 weeks of study intervention for stable or active nonsegmental vitiligo in the previous study to be eligible. The trial aims to evaluate the long-term safety and tolerability of ritlecitinib at dosages of 100 mg and 50 mg once daily.

The clinical trial is a **Phase 3** randomized, double-blind, controlled study designed to evaluate the long-term safety and tolerability of **ritlecitinib tosilate** in adult and adolescent participants with **nonsegmental vitiligo**. The trial will involve a randomized withdrawal and dose-up titration approach, with participants receiving either 100 mg or 50 mg of ritlecitinib daily. The study is expected to commence recruitment on January 31, 2024, and conclude by August 7, 2026, with a total duration of approximately 52 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age and previous completion of a related study. The baseline visit and first dose administration must occur within 30 days following the completion of the prior study. Subsequent follow-up visits will be scheduled to monitor the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and any clinically significant laboratory abnormalities. The primary endpoint focuses on the safety profile, while secondary endpoints include various measures of vitiligo improvement, such as T-VASI75 and F-VASI75 responses.

The expected length of participant involvement is 52 weeks, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. Participants must agree to refrain from using other treatments for vitiligo during the study period. The trial will employ oral administration of the investigational product, with a maximum daily dose of 100 mg for ritlecitinib. The study will also utilize a placebo control to ensure the reliability of the results. The trial is not classified as low intervention, reflecting its comprehensive design and rigorous monitoring requirements.

The clinical trial involves the administration of **Ritlecitinib Tosilate**, an experimental medication provided in the form of a hard capsule. The active substance, **Ritlecitinib Tosilate**, is a chemical compound developed by Pfizer Inc. The medication is administered orally with a maximum daily dose of 100 mg, and the total dose over the treatment period can reach up to 36,400 mg. The treatment duration is set for a maximum of 52 weeks. The primary objective of the trial is to evaluate the long-term safety and tolerability of Ritlecitinib in adult and adolescent participants with nonsegmental vitiligo.

In addition to the experimental medication, the trial includes a placebo control, which is a capsule designed to match the appearance of the Ritlecitinib 50 mg and 100 mg capsules. These placebo capsules do not contain any active substance and are used to maintain the blinding of the study. The placebo is administered orally, following the same dosing schedule as the active treatment, to ensure consistency in the administration process.

**Dexamethasone** is also utilized in the study as a non-experimental treatment. It is provided in tablet form and is administered orally. The maximum daily dose of Dexamethasone is 4 mg, with a total dose limit of 96 mg over a 12-week period. Dexamethasone serves as an auxiliary treatment to manage any potential inflammatory responses during the trial.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. This monitoring is crucial for maintaining the integrity of the trial data and ensuring the reliability of the study outcomes.

The efficacy of **Ritlecitinib** in the treatment of nonsegmental vitiligo will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events leading to discontinuation, as well as the incidence of clinically significant laboratory abnormalities. These endpoints are crucial for evaluating the safety profile of the treatment.

Secondary endpoints will include various measures of response based on the Vitiligo Area Scoring Index (VASI). Specifically, the trial will assess the response based on T-VASI75, F-VASI75, T-VASI50, and F-VASI50, which are defined as at least 75% and 50% improvement from baseline, respectively. Additionally, the trial will evaluate the percent change from baseline in both T-VASI and F-VASI at all time points specified in the Schedule of Assessments (SoA). Further response criteria include stabilization of the disease, defined as less than a 15-point increase in T-VASI from baseline after Week 8, and improvements in Patient Global Impression of Severity for both face (PGIS-F) and vitiligo (PGIS-V).

These efficacy parameters will be measured at all time points outlined in the SoA, allowing for a comprehensive analysis of the treatment's impact over time. The use of validated scales such as VASI and patient-reported outcomes like PGIS ensures that the assessments are both reliable and relevant to the participants' experiences. The trial is designed to provide a thorough evaluation of the long-term efficacy and safety of Ritlecitinib in this patient population.