Anti-IL-4Rα antibody SHR-1819 for moderate-to-severe atopic dermatitis: a randomized phase 2 study.

BACKGROUND

SHR-1819 is a novel monoclonal antibody targeting IL-4Rα, developed for the treatment of type 2 inflammatory diseases such as atopic dermatitis (AD). This phase 2 study aimed to evaluate SHR-1819 for treating moderate-to-severe AD.

METHODS

Patients with an Eczema Area and Severity Index (EASI) score ≥ 16, an Investigator's Global Assessment (IGA) score ≥ 3, and ≥ 10% body surface area affected by AD were randomized (1:1:1:1) to receive SHR-1819 at 300 mg every 2 weeks (Q2W), 600 mg Q2W, 600 mg every 4 weeks (Q4W), or placebo for 16 weeks. Patients were required to use topical moisturizer at least 7 days before randomization, twice daily, and continuously throughout the entire study period. Primary endpoint was the proportion of patients achieving a ≥ 75% reduction from baseline in EASI score (EASI-75) at week 16.

RESULTS

A total of 157 patients received treatment (n = 39, 40, and 41 in the SHR-1819 300 mg Q2W, 600 mg Q2W, and 600 mg Q4W groups; n = 37 in the placebo group). At week 16, the EASI-75 rate was numerically higher in the SHR-1819 groups, compared with the placebo group (69.2% [95% CI: 53.6%-81.4%] at 300 mg Q2W, 75.0% [95% CI: 59.8%-85.8%] at 600 mg Q2W, and 85.4% [95% CI: 71.6%-93.1%] at 600 mg Q4W vs. 37.8% [95% CI: 24.1%-53.9%]; all nominal p < 0.01). Compared with placebo, more patients treated with SHR-1819 achieved IGA score 0-1 and ≥ 2 points reduction, and had ≥ 4 points reduction in weekly average daily Peak Pruritus Numerical Rating Scale score. Treatment-related adverse events (TRAEs) were comparable between the SHR-1819 and placebo groups (45.8% vs. 40.5%). The most common TRAE with SHR-1819 was injection site reaction (10.8%), increased blood bilirubin (5.8%), and conjunctivitis (5.0%). Dose-proportional increases in SHR-1819 concentrations were observed within the studied range. SHR-1819 revealed notable reductions in thymus and activation-regulated chemokine, immunoglobulin E, and eotaxin-3 levels across all doses.

CONCLUSIONS

SHR-1819 demonstrated promising efficacy in improving the signs and symptoms of AD, with a well-tolerated safety profile and favorable pharmacokinetic, and pharmacodynamic characteristics.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05549947; registered on September 22, 2022.