Rademikibart monotherapy for moderate-to-severe atopic dermatitis in a 1-year, randomized, phase II trial (SEASIDE CHINA): initial two-week dosing, followed by two-week or four-week dosing.

Background: Rademikibart (CBP-201) is a potent, next-generation, optimized IL-4Rα-targeting antibody.

Objectives: To evaluate rademikibart efficacy and safety, initially dosed every other week (Q2W), and Q2W or every fourth week (Q4W) from Week 16, in Chinese adults/adolescents with moderate-to-severe atopic dermatitis (AD).

Methods: SEASIDE CHINA (NCT05017480) was a phase II trial: Stage 1 (16-week treatment period), Stage 2 (36-week treatment and 8-week follow-up periods). The primary endpoint was the proportion of patients with a vIGA score 0/1 and ≥2-point reduction from baseline at Week 16. Overall, 330 patients were randomized (2:1) double-blind to receive subcutaneous rademikibart, 600 mg on Day 1 and 300 mg Q2W from Week 2-14, or placebo. Pre-dose at Week 16, patients were assessed for minimally important change (≥50% Eczema Area and Severity Index score reduction, EASI-50) and re-randomized (1:1) double-blind to rademikibart 300 mg Q2W or Q4W.

Results: In Stage 1, 29.0% of patients attained vIGA0/1 and ≥2-point reduction with rademikibart Q2W (p<0.001; 5.9% with placebo) at Week 16, without plateauing. Rapid, significant improvements were also observed with all other rating scales in Stage 1, including EASI-75 (58.6% vs 22.6%) and PP-NRS ≥4-point reduction (36.3% vs 10.5%) with rademikibart Q2W vs placebo, respectively, at Week 16. In Stage 2, Week 16 EASI-50 responders from Stage 1 continued to improve through Week 52 when treated with rademikibart Q2W or Q4W, including vIGA0/1 (59.1%, 62.6%), EASI-75 (84.6%, 84.8%), and PP-NRS ≥4-point reduction (60.4%, 70.3%). Most patients with improvements during rademikibart Q2W therapy at Week 16 maintained these responses through Week 52 in both rademikibart Q2W and Q4W groups: vIGA0/1 (78.0%, 87.1%), EASI-75 (90.1%, 92.3%), PP-NRS ≥4-point reduction (85.3%, 94.8%). Injection site reactions were Grade 1 (mild). No serious TEAEs were treatment related. Three patients discontinued rademikibart due to TEAEs (AD flare, vitiligo, pregnancy).

Conclusions: Rademikibart Q2W induced rapid improvements in AD lesions and pruritus during the initial 16 weeks, which were maintained/improved further with rademikibart Q2W or Q4W across an additional 36 weeks. Rademikibart Q2W and Q4W were similarly efficacious and well tolerated. These findings are compatible with those from the published WW001 international phase II rademikibart trial.