A Phase 2b Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Ritlecitinib in Adult Participants with Chronic Spontaneous Urticaria

The primary objective of this study is to evaluate the efficacy of ritlecitinib by comparing its effect on the improvement of the Urticaria Activity Score 7 (UAS7) at week 12 in adults with chronic spontaneous urticaria. Secondary objectives include assessing the impact of the investigational product on itch, hives, and the achievement of minimal clinically important difference (MCID) in UAS7. Additionally, the study evaluates the rates of complete resolution of disease activity, itch, and hives, as well as the time required to achieve minimal residual disease activity or severity. The safety and tolerability of ritlecitinib are also assessed.

The study involves 104 participants diagnosed with chronic spontaneous urticaria. The study population consists of adults, aged between 18 and 64 years, including both males and females. Participants must have a clinical diagnosis of the condition for at least 3 months at the time of screening. Inclusion requires that individuals remain symptomatic despite the use of second-generation H1-antihistamines at locally approved doses or higher. The cohort includes individuals who are either anti-IgE-naïve or have previous experience with anti-IgE therapies, such as those who discontinued treatment due to intolerance or inadequate response. The primary objectives are to compare the effect of ritlecitinib on the improvement of the UAS7 score at Week 12 and to evaluate the safety and tolerability of the investigational product.

This Phase 2b, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, and tolerability of ritlecitinib tosilate in adults with chronic spontaneous urticaria. The methodology involves a 12-week initial treatment period followed by a 12-week double-blind extension. Participants are expected to undergo a screening visit to confirm a clinical diagnosis of the condition for at least 3 months and to ensure symptomatic status despite the use of second-generation H1-antihistamines. The primary endpoint is the change from baseline in the UAS7 score at Week 12. Secondary endpoints include assessments of ISS7, HSS7, and the incidence of treatment-emergent adverse events. Loratadine is utilized as a background medication. Total participant involvement spans the initial treatment phase and the subsequent extension period.

Ritlecitinib tosilate is an experimental medication administered as a hard capsule. The investigative treatment is delivered via the oral route at dosages of either 50 mg or 100 mg.

A placebo is utilized as a comparator in the study. The placebo is provided in forms matching the 50 mg and 100 mg doses of the active substance.

Loratadine is employed as an auxiliary treatment. This substance is administered at a dose of 10 mg via the oral route.

The primary efficacy endpoint is the change from baseline in the Urticaria Activity Score 7 (UAS7) at Week 12. Secondary efficacy assessments include the change from baseline in UAS7 at all scheduled timepoints excluding Week 12, the change from baseline in the itch severity score 7 (ISS7) at Week 12, and the change from baseline in the hives severity score 7 (HSS7) at Week 12.

Additional efficacy parameters involve the evaluation of clinical responses at Week 12, specifically:

• The proportion of participants achieving a complete response, defined as UAS7 = 0, ISS7 = 0, or HSS7 = 0.
• The proportion of participants achieving a UAS7 ≤ 6.
• The time to response, measured by the time required to achieve a UAS7 ≤ 6 or an improvement from baseline of ≥10 in UAS7.