Description of the 3 Tranquillo Phase 3 clinical program study designs to assess ritlecitinib treatment in adults and adolescents with nonsegmental vitiligo

Abstract

No systemic treatments are currently approved for nonsegmental vitiligo (NSV). In a Phase 2b study (NCT03715829), the JAK3/TEC family kinase inhibitor ritlecitinib 50 mg (± a 100- or 200-mg loading dose) once-daily (QD) was effective and well tolerated in adults with active NSV over 48 weeks. Here we present an overview of the Tranquillo program, which comprises 3 Phase 3 studies examining ≈2050 patients across 17 countries, aiming to evaluate the efficacy, safety, and tolerability of ritlecitinib 50 mg and 100 mg QD in adults and adolescents with NSV.  Tranquillo (NCT05583526) is a randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of ritlecitinib 50 mg vs placebo over 52 weeks. The Tranquillo long-term extension (LTE; NCT06163326), a randomized, double-blind, withdrawal and dose-up titration study, investigates the safety, tolerability, and efficacy of ritlecitinib 50 mg and 100 mg and durability of response of ritlecitinib 50 mg following participation in Tranquillo for 52 weeks. Tranquillo 2 (NCT06072183) contains Part I, a 52-week randomized, double-blind, placebo-controlled study with a 52-week extension with randomized dose-up/dose-down titration comparing ritlecitinib 50 mg and 100 mg vs placebo, and Part II, a de novo 52-week open-label ritlecitinib 100 mg arm to support the safety database. Patients are aged ≥12 years (Tranquillo 2: ≥18 years) with active or stable NSV for ≥3 months, body surface area (BSA) involvement of 4% to 60%, facial BSA ≥0.5%, Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5, and Total (T)-VASI ≥3 in all 3 studies. Tranquillo will enroll ≈600 patients from ≈115 locations globally. The primary efficacy endpoint is the proportion of patients achieving ≥75% improvement in F-VASI from baseline (F-VASI75) at Week 52; T-VASI50 at Week 52 is a co-primary efficacy endpoint in the US and a key secondary endpoint globally (other than the US). Tranquillo LTE will enroll ≈400 patients who have completed the Tranquillo study. The primary endpoint is safety. Secondary endpoints include percent change from baseline in F-VASI and T-VASI and the proportion of patients achieving F-VASI50/75/90/100 and T-VASI50/75/90/100 at Weeks 4, 8, 12, 24, 36, and 52. Tranquillo 2 will simultaneously enroll ≈1000 patients in Part I and ≈450 patients in Part II from ≈230 locations globally. The primary efficacy endpoint is the proportion of patients achieving F-VASI75 at Week 52; T-VASI50 at Week 52 is a co-primary efficacy endpoint in the US and a key secondary endpoint globally (other than US). In all 3 studies, the safety and tolerability of ritlecitinib will be assessed at all time points. Overall, the Phase 3 Tranquillo program explores the efficacy, safety, and tolerability of ritlecitinib, a targeted systemic treatment, in a large cohort of patients with NSV over the course of up to 104 weeks.