The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-co

Abstract

SummaryBackground The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about À50% at week 4 with CIM331 compared with À20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies

“…The first phase I study revealed a statistically significant 50% reduction in itch, assessed by the pruritus visual analogue scale, 4 weeks after initiation of treatment compared to the placebo group (20% reduction) [57]. Moreover, nemolizumab decreased sleep disturbance and use of topical hydrocortisone.…”

T helper type 2 signatures in atopic dermatitis

“…45,114 In addition, the anti-IL-31 receptor A antibody nemolizumab successfully resolves atopic itch. 57,115 Despite the safety and the considerable effectiveness of these biologics, there still exists high and low responders. This fact reiterates the heterogeneity of AD.…”

Biological Therapeutic Treatment of Atopic Dermatitis

“…По данным Nobbe и соавт., в воспалительном инфильтрате биоптатов кожи больных АД определяется повышенный уровень ИЛ-31 по сравнению со здоровой кожей и кожей больных другими воспалительными заболеваниями [98]. Экспериментальными исследованиями отмечен значи-мый вклад ИЛ-31 в индукцию кожного зуда у больных АД [99,100]. В работе Dillon и соавт., у трансгенных мышей на фоне гиперэкспрессии ИЛ-31 развивались кожные высыпания, сходные с таковыми при АД и пруриго [101].…”