Ritlecitinib Generally Well-Tolerated in Pediatric Patients with Alopecia, According to Phase 1 Study

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A phase 1 study measured the pharmacokinetic and safety parameters in pediatric patients being treated with ritlecitinib for alopecia.¹ Patients under the age of 12 experienced little to no adverse effects with no laboratory abnormalities.

The phase 1, single-group, uncontrolled, interventional, open-label study (NCT05650333) included 14 patients between the ages of 6 to 12. The mean age of 8.5 years and 60% of participants were aged 6 to < 9 years. Additionally, most of the participants were female. All were clinically diagnosed with severe alopecia, equating to ≥ 50% scalp hair loss according to the Severity of Alopecia Tool score. Participants also had no evidence of terminal hair growth within the previous year.

Throughout the study, each patient received 20 mg of ritlecitinib once a day for 7 days. The first and last dosages were provided in-office while all others were administered at home. Safety follow-up phone visits occurred between 28 to 35 days after the last dose. Blood and urine samples were also collected at a few time points on day 7.

Investigators measured the area under the concentration-time curve from 0 to 24 hours, maximum concentration and time to reach, apparent clearance and volume of distribution, and terminal half-life. They also evaluated the safety and tolerability of the drug.

The median time to maximum plasma concentration on day 7 was ~0.5 hours. The mean half-life was ~1.19 hours. Geometric mean values and variability for exposure parameters AUC₂₄ and C_max were 437.5 ng∙h/mL, 30% and 208.7 ng/mL, 38%, respectively. Furthermore, mean CL/F was 45.7 L/h, and V_z/F was ~74.9 L.

“[Pharmacokinetic] results will be used to update the population PK model established based on prior studies in adults and adolescents, and subsequently to guide the dosing selection in pediatric phase 3 studies,” the authors wrote.

Some adverse events were experienced in 3 patients. Mild vomiting, nausea, and myalgia occurred but these were not related to treatment. Dosing was not interrupted or changed because of these. A case of moderate urticaria on both legs led to a participant discontinuing the drug after 3 days. However, no severe adverse effects or laboratory abnormalities were reported.

Alopecia can develop at any age but 40% of patients first demonstrate symptoms before the age of 20. Pediatric patients exhibit negative impacts on their quality of life, which has been proven in adult patients in the ALLEGRO-2b and 3 trial and other studies. Specifically, children may experience increased anxiety, depression, and obsessive-compulsive disorder, which can affect self-esteem, relationships, body image, and academic performance.² In another study, nearly 80% of participants between the ages of 5 and 11 years said that they were bullied because of their alopecia.³

Ritlecitinib, a JAK3/TEC family kinase inhibitor, was approved in June 2023 to treat adults and adolescents with severe alopecia aged 12 years and over. Currently, there are no systemic treatments approved for this younger age group. Future studies will continue to assess the safety and efficacy of ritlecitinib in younger pediatric patients with alopecia.

References

1. Gonzalez ME, Browning J, Smith S, et al. A Phase 1, Open-Label Study of the Pharmacokinetics of Ritlecitinib in Children Aged 6-12 Years With Alopecia Areata. Pediatr Dermatol. Published online February 9, 2025. doi:10.1111/pde.15895 

2. Sejdiu Z, Hess S, Jafferany M. Psychosocial comorbidities in patients with pediatric alopecia areata: a literature review. Clin Exp Dermatol. 2024;49(10):1118-1124. doi:10.1093/ced/llae188

3. Christensen T, Yang JS, Castelo-Soccio L. Bullying and Quality of Life in Pediatric Alopecia Areata. Skin Appendage Disord. 2017;3(3):115-118. doi:10.1159/000466704