PMID- 32651105
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20210607
IS  - 1873-569X (Electronic)
IS  - 0923-1811 (Linking)
VI  - 99
IP  - 2
DP  - 2020 Aug
TI  - Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a 
      fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to 
      severe atopic dermatitis.
PG  - 82-89
LID - S0923-1811(20)30201-2 [pii]
LID - 10.1016/j.jdermsci.2020.06.005 [doi]
AB  - BACKGROUND: KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential 
      novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting 
      the immunopathogenic pathways. OBJECTIVE: Assess the safety and tolerability of 
      repeated doses of KHK4083 in patients with moderate to severe AD, and investigate 
      the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the 
      clinical efficacy and pharmacodynamics as exploratory objectives. METHODS: In 
      this phase 1, single-center, open-label, repeated-dose study, a total of 22 
      patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were 
      followed until Day 155. RESULTS: There were no deaths, serious adverse events 
      (SAEs), or discontinuations due to adverse events (AEs). Common 
      treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and 
      chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory 
      values, vital signs, and electrocardiogram recordings were observed. The C(max) 
      was 267 +/- 53 mug/mL and the t(1/2) was 303 +/- 88 h at Day 29. The overall 
      assessment of antibodies against KHK4083 (immunogenicity) showed low positive 
      responses. Continued improvement in the Eczema Area and Severity Index (EASI) and 
      Investigator's Global Assessment (IGA) scores were observed throughout the study. 
      The mean and median percent changes in thymus and activation-regulated chemokine 
      (TARC) continued to decrease over time to -70.4 and -78.8 % until Day 155. 
      CONCLUSION: Repeated intravenous infusion of KHK4083 had an acceptable safety 
      profile in patients with moderate to severe AD. Sustained improvement in the 
      symptoms of AD was observed after completion of KHK4083 treatment.
CI  - Copyright (c) 2020 Japanese Society for Investigative Dermatology. Published by 
      Elsevier B.V. All rights reserved.
FAU - Nakagawa, Hidemi
AU  - Nakagawa H
AD  - Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan. 
      Electronic address: hidemi@jikei.ac.jp.
FAU - Iizuka, Hajime
AU  - Iizuka H
AD  - Medical Corporation Kojinkai Hosui Sogo Medical Clinic, Sapporo, Japan.
FAU - Nemoto, Osamu
AU  - Nemoto O
AD  - Medical Corporation Kojinkai Hosui Sogo Medical Clinic, Sapporo, Japan.
FAU - Shimabe, Munetake
AU  - Shimabe M
AD  - Kyowa Kirin Co., Ltd, Tokyo, Japan.
FAU - Furukawa, Yasunobu
AU  - Furukawa Y
AD  - Kyowa Kirin Co., Ltd, Tokyo, Japan.
FAU - Kikuta, Natsuko
AU  - Kikuta N
AD  - Kyowa Kirin Co., Ltd, Tokyo, Japan.
FAU - Ootaki, Kenji
AU  - Ootaki K
AD  - Kyowa Kirin Co., Ltd, Tokyo, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20200613
PL  - Netherlands
TA  - J Dermatol Sci
JT  - Journal of dermatological science
JID - 9011485
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (KHK4083)
RN  - 0 (OX40 Ligand)
RN  - 0 (TNFSF4 protein, human)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects
MH  - Chills/chemically induced/*epidemiology/immunology
MH  - Dermatitis, Atopic/diagnosis/*drug therapy/immunology
MH  - Drug Administration Schedule
MH  - Female
MH  - Fever/chemically induced/*epidemiology/immunology
MH  - Humans
MH  - Infusions, Intravenous
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - OX40 Ligand/antagonists & inhibitors/immunology
MH  - Severity of Illness Index
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Atopic dermatitis
OT  - OX40
OT  - Phase 1
COIS- Declaration of Competing Interest H.N, the consultant of this study, received 
      consultant fees, research grants, and speaker honoraria from for Kyowa Kirin Co., 
      Ltd. H.I and O.N are the investigators of this study and declares no conflict of 
      interests. M.S, Y.F, N.K and K.O are employees of Kyowa Kirin Co., Ltd. This work 
      was funded and supported by Kyowa Kirin Co., Ltd.
EDAT- 2020/07/12 06:00
MHDA- 2021/06/08 06:00
CRDT- 2020/07/12 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/06/04 00:00 [revised]
PHST- 2020/06/09 00:00 [accepted]
PHST- 2020/07/12 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2020/07/12 06:00 [entrez]
AID - S0923-1811(20)30201-2 [pii]
AID - 10.1016/j.jdermsci.2020.06.005 [doi]
PST - ppublish
SO  - J Dermatol Sci. 2020 Aug;99(2):82-89. doi: 10.1016/j.jdermsci.2020.06.005. Epub 
      2020 Jun 13.