PMID- 26409172
OWN - NLM
STAT- MEDLINE
DCOM- 20161214
LR  - 20220408
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 174
IP  - 2
DP  - 2016 Feb
TI  - 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-controlled study.
PG  - 296-304
LID - 10.1111/bjd.14207 [doi]
AB  - 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.
CI  - (c) 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons 
      Ltd on behalf of British Association of Dermatologists.
FAU - Nemoto, O
AU  - Nemoto O
AD  - Kojinkai, Kita13-Jo Naika-Hifuka Clinic, Hokkaido, Japan.
FAU - Furue, M
AU  - Furue M
AD  - Department of Dermatology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Nakagawa, H
AU  - Nakagawa H
AD  - Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Shiramoto, M
AU  - Shiramoto M
AD  - Medical Co. LTA Hakata Clinic, Fukuoka, Japan.
FAU - Hanada, R
AU  - Hanada R
AD  - Medical Co. LTA Sumida Hospital, Tokyo, Japan.
FAU - Matsuki, S
AU  - Matsuki S
AD  - Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
FAU - Imayama, S
AU  - Imayama S
AD  - Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
FAU - Kato, M
AU  - Kato M
AD  - Kojinkai, Kita13-Jo Naika-Hifuka Clinic, Hokkaido, Japan.
FAU - Hasebe, I
AU  - Hasebe I
AD  - Kojinkai, Kita13-Jo Naika-Hifuka Clinic, Hokkaido, Japan.
FAU - Taira, K
AU  - Taira K
AD  - Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
FAU - Yamamoto, M
AU  - Yamamoto M
AD  - Translational Clinical Research Division, Chugai Pharmaceutical Co., Ltd., Tokyo, 
      Japan.
FAU - Mihara, R
AU  - Mihara R
AD  - Translational Clinical Research Division, Chugai Pharmaceutical Co., Ltd., Tokyo, 
      Japan.
FAU - Kabashima, K
AU  - Kabashima K
AD  - Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Ruzicka, T
AU  - Ruzicka T
AD  - Department of Dermatology and Allergology, Ludwig-Maximilian-University Munich, 
      Munich, Germany.
FAU - Hanifin, J
AU  - Hanifin J
AD  - Department of Dermatology, Oregon Health and Science University, Portland, OR, 
      U.S.A.
FAU - Kumagai, Y
AU  - Kumagai Y
AD  - Kitasato University School of Medicine, Kitasato Clinical Research Center, 
      Kanagawa, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20151219
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (IL31RA protein, human)
RN  - 0 (Receptors, Interleukin)
RN  - GN465U8B72 (nemolizumab)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Dermatitis, Atopic/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Healthy Volunteers
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Pruritus/drug therapy
MH  - Receptors, Interleukin/*immunology
MH  - Sleep Wake Disorders/drug therapy/etiology
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2015/09/27 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/09/27 06:00
PHST- 2015/09/22 00:00 [accepted]
PHST- 2015/09/27 06:00 [entrez]
PHST- 2015/09/27 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1111/bjd.14207 [doi]
PST - ppublish
SO  - Br J Dermatol. 2016 Feb;174(2):296-304. doi: 10.1111/bjd.14207. Epub 2015 Dec 19.