Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Ritlecitinib Efficacy and Safety in Pediatric Patients with Severe Alopecia Areata

The primary objective of this study is to evaluate the efficacy of ritlecitinib compared to placebo regarding the regrowth of lost scalp hair in pediatric participants with alopecia areata. Secondary objectives include:

• Assessment of hair regrowth at all study visits.
• Evaluation of patient-centered outcomes using the Patient's Global Impression of Change (PGI-C) and Alopecia Areata Patient Priority Outcomes (AAPPO) scales.
• Measurement of psychological and social impairment via the Patient-Reported Outcomes Measurement Information System (PROMIS), Behavior Rating Inventory of Executive Function (BRIEF2), and the modified Children’s Dermatology Life Quality Index (CDLQI).
• Evaluation of response rates in eyebrow assessment (EBA) and eyelash assessment (ELA).
• Characterization of the pharmacokinetics of ritlecitinib.
• Assessment of safety, tolerability, and the acceptability and palatability of the age-appropriate formulation.

This clinical trial involves a total of 157 pediatric participants, including both males and females. The study population consists of patients diagnosed with alopecia areata, encompassing subtypes such as alopecia totalis and alopecia universalis. Eligible participants are between 6 and 11 years of age at the time of screening and must demonstrate a SALT score of 50 or greater, indicating at least 50% loss of scalp hair. Additionally, individuals must have no evidence of terminal hair regrowth within the preceding 12 months and a documented history of clinical response failure to previous treatments, including topical therapies, off-label pharmacologic interventions, or hairpiece prosthetics.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to investigate the efficacy and safety of ritlecitinib in pediatric participants aged 6 to less than 12 years with alopecia areata. Participants will be assigned to receive either ritlecitinib or a matching placebo. The primary objective is to evaluate the regrowth of lost scalp hair, specifically measured by the achievement of an absolute SALT score of ≤10 at Week 24. Secondary endpoints include assessments of the PGI-C response, changes in various clinical scales, and the monitoring of treatment-emergent adverse events. The study sequence begins with a screening visit to confirm eligibility, followed by a baseline visit. Subsequent visits will involve periodic monitoring of clinical responses and safety parameters throughout the treatment period. The study involves the evaluation of plasma concentration of the active substance at specific intervals. Participant involvement is determined by the clinical follow-up schedule required to reach the defined endpoints.

The experimental treatment consists of ritlecitinib tosilate, administered as a hard capsule via the oral route. The investigational product is provided in two specific strengths: 30 mg and 50 mg.

A placebo is utilized to match the respective strengths of the experimental medication. This includes a placebo corresponding to the 30 mg dose and a placebo corresponding to the 50 mg dose.

The efficacy of ritlecitinib will be assessed in pediatric participants with alopecia areata. The primary endpoint is the response rate defined by achieving an absolute SALT score of ≤10 at Week 24.

Secondary efficacy parameters include:

• PGI-C response, categorized as “moderately improved” or “greatly improved,” at Week 24 and at all other scheduled visits.
• Change from baseline in SALT score and response rates based on absolute SALT scores of ≤10 or ≤20 at all visits.
• Response based on improvement from baseline for each AAPPO Item.
• Change from baseline in AAPPO activity limitation and emotional symptoms scores, as well as PROMIS Parent Proxy Depressive Symptoms T-score and PROMIS Parent Proxy Anxiety Symptoms T-score at all visits.
• Change from baseline in BRIEF®2 T-scores for the Behavior Regulation Index, Emotional Regulation Index, and Cognitive Regulation Index, alongside change from baseline in the modified CDLQI total score at all visits.
• Response based on achieving at least a 2-grade improvement or an EBA score of 3 at all visits for participants with an abnormal baseline EBA.
• Response based on achieving at least a 2-grade improvement or an ELA score of 3 at all visits for participants with an abnormal baseline ELA.
• Plasma concentration of ritlecitinib measured at 1 hour and 3 hours post-dose at Week 4 or Week 8.
• Assessment of acceptability and palatability.