B7981028 - A LONG-TERM, DOUBLE-BLIND EXTENSION STUDY TO INVESTIGATE THE SAFETY AND EFFICACY OF RITLECITINIB IN PARTICIPANTS WITH SEVERE ALOPECIA AREATA WHO PREVIOUSLY COMPLETED STUDIES B7981027 OR B7981031

The primary objective is to evaluate the long-term safety and tolerability of ritlecitinib in pediatric participants with severe alopecia areata who have completed the studies B7981027 or B7981031. This objective is clinically relevant for assessing the extended safety profile of ritlecitinib in the pediatric population with severe alopecia areata, a condition characterized by extensive hair loss that can significantly impact quality of life.

The secondary objectives include:

• To evaluate the long-term efficacy of ritlecitinib and durability of response in pediatric participants with severe alopecia areata who have completed the studies B7981027 or B7981031.

• To evaluate change in psychological/psychosocial status and neuro-psychological/cognitive development status.

This long-term extension trial enrolled a total of **62 participants** with severe **alopecia areata**, including **alopecia totalis** and **alopecia universalis**. The study population consisted of **pediatric participants** of both **male** and **female** gender who had completed previous clinical studies (B7981027 or B7981031) evaluating ritlecitinib. Participants were selected based on their completion of the preceding trials, with those originating from Study B7981031 required to demonstrate at least 50% scalp hair loss, corresponding to a **SALT score** of ≥50 at both Screening and Baseline visits. The trial involved a **vulnerable population**, reflecting the pediatric nature of the study cohort. The sponsor did not provide information regarding specific lifestyle considerations such as diet, physical activity, or habits of the participants.

This is a **Phase 3**, **long-term**, **double-blind** extension study designed to evaluate the safety and efficacy of **ritlecitinib** in pediatric participants with severe **alopecia areata** who have previously completed prior studies B7981027 or B7981031. The primary objective is to assess the long-term safety and tolerability of ritlecitinib in this patient population. The study will investigate the use of **ritlecitinib tosilate** administered as **hard capsules** via the **oral** route, with two dosing regimens of 30 mg and 50 mg daily. **Placebo** formulations matching both dose strengths will also be utilized to maintain blinding. The maximum daily dose is 50 mg, with a maximum total dose of 54,750 mg over the treatment period. The active substance is a small molecule drug of chemical origin, manufactured by Pfizer Inc.

Participants eligible for enrollment include those with alopecia areata, including **alopecia totalis** and **alopecia universalis**, who have completed the preceding studies. For participants originating from Study B7981031, eligibility requires at least 50% scalp hair loss due to alopecia areata, defined as a **Severity of Alopecia Tool (SALT)** score of 50 or greater at both screening and baseline visits. Participants from Study B7981027 who completed that study are also eligible for enrollment. The study will enroll participants with severe alopecia areata to assess long-term outcomes following prior treatment exposure.

The primary endpoints focus on safety assessment and include the incidence of **treatment-emergent adverse events**, the incidence of **serious adverse events**, and adverse events leading to permanent discontinuation from the study. Secondary endpoints evaluate efficacy measures including response rates based on achieving absolute SALT scores of 10 or less and 20 or less at all visits, as well as change from baseline in SALT score at all visits. Additional secondary endpoints assess **eyebrow assessment (EBA)** score and **eyelash assessment (ELA)** score responses, defined as at least 2 grade improvement or a score of 3 in participants with abnormal baseline assessments. **Patient Global Impression of Change (PGI-C)** response, defined as a score of "moderately improved or greatly improved," will be evaluated at all time points.

Patient-reported outcomes will be assessed through changes from baseline in **PROMIS Parent Proxy Depressive Symptoms** T-score and **PROMIS Parent Proxy Anxiety Symptoms** T-score at all visits. The study will also evaluate changes from baseline in **Behavior Rating Inventory of Executive Function 2 (BRIEF 2)** T-scores for three index scores: **Behavior Regulation Index**, **Emotional Regulation Index**, and **Cognitive Regulation Index** at all visits. Quality of life measures include change from baseline in modified **Children's Dermatology Life Quality Index (CDLQI)** total score at all visits. Cognitive assessment will be performed using the **Wechsler Intelligence Scale for Children Fifth Edition (WISC-V)** at the end of study at Month 36.

The overall trial duration is estimated to extend from May 2026 to May 2030, with recruitment anticipated to begin in May 2026 and the study expected to conclude in May 2030. The maximum treatment period for individual participants is 36 months, during which participants will receive continuous study medication. Participants will attend scheduled study visits throughout the treatment period for safety monitoring, efficacy assessments, and collection of patient-reported outcomes. The study design includes a screening visit to confirm eligibility, followed by a baseline visit where treatment is initiated. Regular follow-up visits will occur throughout the 36-month treatment period to assess safety parameters, measure hair regrowth using standardized assessment tools, and evaluate quality of life and psychological outcomes. The end-of-study visit will occur at Month 36 or upon early termination. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, adverse events requiring discontinuation, participant withdrawal of consent, or investigator decision based on safety concerns.

The experimental medication evaluated in this clinical trial is ritlecitinib tosilate, a small molecule drug manufactured by Pfizer Inc. and identified by the sponsor product code PF-06651600. Ritlecitinib tosilate is formulated as a hard capsule for oral administration. The active substance is ritlecitinib tosilate, which is of chemical origin. Two dosage strengths are utilized in the study: 30 mg and 50 mg hard capsules. The maximum daily dose is 30 mg for the lower strength formulation and 50 mg for the higher strength formulation. The maximum total dose over the treatment period is 32,850 mg for the 30 mg formulation and 54,750 mg for the 50 mg formulation. The maximum treatment period is 36 months for both dosage strengths.

The study incorporates placebo comparators designed to match the experimental medication. Two placebo formulations are included: placebo to match ritlecitinib 30 mg and placebo to match ritlecitinib 50 mg. These placebo products are manufactured to correspond to the respective active treatment capsules to maintain blinding in this double-blind extension study. The placebo formulations contain no active pharmaceutical ingredient and serve as control treatments to enable comparison with the experimental medication.

Efficacy will be assessed through multiple parameters evaluating hair regrowth, patient-reported outcomes, and quality of life measures. The primary efficacy endpoints include response based on achieving an absolute Severity of Alopecia Tool (SALT) score of ≤10 at all visits and response based on achieving an absolute SALT score of ≤20 at all visits. Additional primary endpoints include change from baseline in SALT score at all visits, response based on achieving at least 2 grade improvement or a score of 3 in eyebrow assessment (EBA) score at all visits in participants with an abnormal EBA at baseline, and response based on achieving at least 2 grade improvement or a score of 3 in eyelash assessment (ELA) score at all visits in participants with an abnormal ELA at baseline. Patient Global Impression of Change (PGI-C) response, defined as a score of "moderately improved or greatly improved" at all time points, will also be evaluated.

Secondary efficacy assessments will include change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Parent Proxy Depressive Symptoms T-score at all visits and change from baseline in PROMIS Parent Proxy Anxiety Symptoms T-score at all visits. Change from baseline in Behavior Rating Inventory of Executive Function®2 (BRIEF®2) T-scores for the three index scores (Behavior Regulation Index, Emotional Regulation Index, Cognitive Regulation Index) will be measured at all visits. Quality of life will be assessed through change from baseline in modified Children's Dermatology Life Quality Index (CDLQI) total score at all visits. Cognitive function will be evaluated using change from baseline in Wechsler Intelligence Scale for Children® Fifth Edition (WISC-V) at end of study (Month 36). The treatment period will extend up to 36 months.