In a phase 2 randomized clinical trial, once-daily oral ICP-332 was associated with reductions in atopic dermatitis severity and pruritus over 4 weeks without serious adverse events in adults with moderate to severe atopic dermatitis. At week 4, mean reductions in Eczema Area and Severity Index were 78% with the 80-mg dose and 73% with the 120-mg dose, compared with 17% with placebo. An Eczema Area and Severity Index 75 response was achieved by 64% of patients in each ICP-332 group vs 8% with placebo, and improvements in pruritus severity and frequency were observed as early as day 2 of treatment.

This double-blind, placebo-controlled phase 2 trial enrolled 75 adults aged 18 to 75 years with a diagnosis of AD for at least 1 year and evidence of moderate to severe disease, defined by an Eczema Area and Severity Index score of 16 or higher, affected body surface area of at least 10%, and a Validated Investigator Global Assessment for Atopic Dermatitis score of 3 or higher. All participants had a documented history of inadequate response to, or contraindication for, topical corticosteroids or topical calcineurin inhibitors. The study was conducted across 19 centers in China between February 6 and November 7, 2023.

Participants were randomized in a 1:1:1 ratio to receive oral ICP-332 at doses of 80 mg or 120 mg, or matching placebo, once daily for 4 weeks. Randomization was stratified by intensive pharmacokinetic sampling, and patients, investigators, and study personnel were blinded to treatment assignment. The primary end point was safety, assessed by the incidence and severity of treatment-emergent adverse events. Secondary efficacy end points included percentage change from baseline in Eczema Area and Severity Index score, proportions of patients achieving predefined response thresholds, changes in pruritus numerical rating scale scores, affected body surface area, and Dermatology Life Quality Index scores.

Among the 74 patients included in the safety analysis, treatment-emergent adverse events occurred in 68% of patients receiving placebo, 76% receiving 80 mg of ICP-332, and 75% receiving 120 mg. All adverse events were classified as mild or moderate. Decreased blood fibrinogen was the most common adverse event and occurred more often in the ICP-332 groups. No serious adverse events or deaths were reported, and one case of rhabdomyolysis in the 120-mg group was determined by investigators to be unrelated to study treatment.

The researchers noted several limitations, including the small sample size and short treatment duration, which limited assessment of long-term efficacy, durability of response, and uncommon adverse events. All enrolled patients were of Asian descent, which may limit generalizability to other populations. The study also did not include active comparators or evaluate treatment effects across specific patient subgroups.

“In this phase 2 randomized clinical trial, ICP-332 monotherapy was efficacious and demonstrated a favorable benefit-risk profile compared with placebo in adults with moderate to severe AD, supporting initiation of larger randomized, controlled, phase 3 studies to confirm its potential as an effective treatment for this population,” noted the lead author Jinhua Xu, PhD, of the Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China, and colleagues.

The study was funded by InnoCare Pharma Tech Co, which participated in the design and conduct of the study, data collection and analysis, and the decision to submit the manuscript. Wei Zhou, PhD, and Danbing Fan, MD, and Yue Du, MS, reported employment with InnoCare Pharma Tech Co, and Wei Zhou, PhD, reported a pending patent (PCT/CN2024/138717,63617161); no additional disclosures were reported.

Source: JAMA Dermatology