Description of the Tranquillo Phase 3 Clinical Trial Designs/Study Protocols to Assess Ritlecitinib in Adults and Adolescents with Nonsegmental Vitiligo

INTRODUCTION: Ritlecitinib is an oral, selective inhibitor of JAK3 and TEC family kinases under investigation for the treatment of nonsegmental vitiligo (NSV). In a phase 2b study, ritlecitinib was efficacious and well tolerated over 48 weeks. The Tranquillo phase 3 program comprises three studies aiming to evaluate the efficacy, safety, and tolerability of once-daily 50-mg and 100-mg ritlecitinib in adult and adolescent patients with NSV. METHODS: Tranquillo (NCT05583526), a randomized, double-blind, placebo-controlled 52-week trial, compares the efficacy and safety of once-daily 50-mg ritlecitinib vs placebo (N ≈ 600). Tranquillo LTE (NCT06163326), a randomized, double-blind, withdrawal and dose-up titration 52-week extension study, investigates the safety, tolerability, and efficacy of once-daily 50-mg and 100-mg ritlecitinib and durability of response with once-daily 50-mg ritlecitinib following participation in Tranquillo (N ≈ 400). Tranquillo 2 (NCT06072183) comprises two parts: Part I, a 52-week randomized, double-blind, placebo-controlled study with 52-week extension with randomized dose-up/dose-down titration comparing once-daily 50-mg and 100-mg ritlecitinib with placebo (N ≈ 1000), and Part II, a de novo 52-week nonrandomized, open-label once-daily 100-mg ritlecitinib arm (N ≈ 450). Participants are aged ≥ 12 years (Tranquillo 2: ≥ 18 years) with clinical diagnosis of active or stable NSV for ≥ 3 months, body surface area involvement 4%-60%, facial body surface area ≥ 0.5%, Facial Vitiligo Area Scoring Index (F-VASI) ≥ 0.5, and Total (T)-VASI ≥ 3. PLANNED OUTCOMES: Tranquillo's primary efficacy endpoint is the proportion of participants achieving ≥ 75% improvement in F-VASI from baseline (F-VASI75) at Week 52; T-VASI50 at Week 52 is a coprimary efficacy endpoint in the US and a key secondary endpoint globally (other than US). Tranquillo LTE's primary endpoint is safety. Tranquillo 2's primary efficacy endpoint is F-VASI75 at Week 52; T-VASI50 at Week 52 is a coprimary efficacy endpoint in the US and a key secondary endpoint globally (other than US). In all three studies, the safety and tolerability of ritlecitinib are assessed throughout. Graphical abstract available for this article. GOV REGISTRATIONS: NCT05583526, NCT06163326, NCT06072183.