O Nemoto1, M Furue2, H Nakagawa3, M Shiramoto4, R Hanada5, S Matsuki6, S Imayama6, M Kato1, I Hasebe1, K Taira6, M Yamamoto7, R Mihara7, K Kabashima8, T Ruzicka9, J Hanifin10, Y Kumagai11. 1. Kojinkai, Kita13-Jo Naika-Hifuka Clinic, Hokkaido, Japan. 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan. 4. Medical Co. LTA Hakata Clinic, Fukuoka, Japan. 5. Medical Co. LTA Sumida Hospital, Tokyo, Japan. 6. Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan. 7. Translational Clinical Research Division, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. 8. Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 9. Department of Dermatology and Allergology, Ludwig-Maximilian-University Munich, Munich, Germany. 10. Department of Dermatology, Oregon Health and Science University, Portland, OR, U.S.A. 11. Kitasato University School of Medicine, Kitasato Clinical Research Center, Kanagawa, Japan.
Abstract
BACKGROUND: 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 -50% at week 4 with CIM331 compared with -20% 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.
RCT Entities:
BACKGROUND: 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 -50% at week 4 with CIM331 compared with -20% 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.
Authors: Angelica V Medina-Cucurella; Gary F Bammert; William Dunkle; Christopher Javens; Yaqi Zhu; Veronica T Mutchler; Janet T Teel; Caitlin A Stein; Steve A Dunham; Timothy A Whitehead Journal: Biochemistry Date: 2020-06-04 Impact factor: 3.162