PMID- 33599356
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1440-1746 (Electronic)
IS  - 0815-9319 (Print)
IS  - 0815-9319 (Linking)
VI  - 36
IP  - 8
DP  - 2021 Aug
TI  - Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in 
      patients with Crohn's disease.
PG  - 2180-2186
LID - 10.1111/jgh.15463 [doi]
AB  - BACKGROUND AND AIM: E6011 is a humanized monoclonal antibody targeting 
      fractalkine (FKN), a CX3C chemokine, which regulates leukocyte trafficking during 
      inflammation. We evaluated the safety and pharmacokinetic profile of E6011 in 
      patients with Crohn's disease (CD) and also performed preliminary pharmacodynamic 
      (PD) and efficacy assessments. METHODS: This study included a 12-week multiple 
      ascending dose (MAD) phase (2, 5, 10, and 15 mg/kg intravenously every 2 weeks, 
      n = 6, 8, 7, and 7, respectively) and a 40-week Extension phase (n = 12) at the 
      same dose as the MAD phase. Serum E6011, serum total FKN (free soluble FKN and 
      E6011-FKN complex) as a PD marker and CD activity index were evaluated. The 
      primary outcome was safety assessment in the MAD phase. RESULTS: Twenty-seven 
      (96%) of 28 patients had previously been treated with anti-tumor necrosis factor 
      alpha agents. During the MAD phase, adverse events (AEs) occurred in 18 (64%). The 
      most common AE was nasopharyngitis (five patients, 18%). No severe AEs occurred. 
      Serious AEs occurred in three patients, progression of CD in two, and anemia in 
      one. Serum E6011 concentrations increased dose-dependently after infusion and 
      reached a plateau around 4-6 weeks. Serum total FKN rose simultaneously. Five 
      (18%) patients developed anti-E6011 antibodies during the study. Overall, 
      clinical response and clinical remission were observed at Week 12 in 40% (10/25) 
      and 16% (4/25) of active CD patients, respectively. CONCLUSION: E6011 was 
      well-tolerated and might be effective in CD patients. These findings need to be 
      clarified in a randomized controlled study.
CI  - (c) 2021 The Authors. Journal of Gastroenterology and Hepatology published by 
      Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons 
      Australia, Ltd.
FAU - Matsuoka, Katsuyoshi
AU  - Matsuoka K
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Keio University School of Medicine, Tokyo, Japan.
FAU - Naganuma, Makoto
AU  - Naganuma M
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Keio University School of Medicine, Tokyo, Japan.
FAU - Hibi, Toshifumi
AU  - Hibi T
AD  - Center for Advanced IBD Research and Treatment, Kitasato University Kitasato 
      Institute Hospital, Tokyo, Japan.
FAU - Tsubouchi, Hirohito
AU  - Tsubouchi H
AD  - Kagoshima City Hospital, Kagoshima, Japan.
FAU - Oketani, Kiyoshi
AU  - Oketani K
AD  - Clinical Development Department, EA Pharma Co., Ltd., Tokyo, Japan.
FAU - Katsurabara, Toshinori
AU  - Katsurabara T
AD  - Clinical Development Department, EA Pharma Co., Ltd., Tokyo, Japan.
FAU - Hojo, Seiichiro
AU  - Hojo S
AD  - Clinical Data Science Department, Medicine Development Center, Eisai Co., Ltd., 
      Tokyo, Japan.
FAU - Takenaka, Osamu
AU  - Takenaka O
AD  - Clinical Pharmacology Science Department, Medicine Development Center, Eisai Co., 
      Ltd., Tokyo, Japan.
FAU - Kawano, Tetsu
AU  - Kawano T
AD  - Research and Development, KAN Research Institute, Inc., Tokyo, Japan.
FAU - Imai, Toshio
AU  - Imai T
AD  - Research and Development, KAN Research Institute, Inc., Tokyo, Japan.
FAU - Kanai, Takanori
AU  - Kanai T
AUID- ORCID: 0000-0002-1466-4532
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Keio University School of Medicine, Tokyo, Japan.
LA  - eng
GR  - EA Pharma Co., Ltd./
GR  - Eisai Co., Ltd./
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210331
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - G8NT4Q571B (quetmolimab)
SB  - IM
MH  - Adult
MH  - *Antibodies, Monoclonal, Humanized/adverse effects/pharmacokinetics/therapeutic 
      use
MH  - *Antirheumatic Agents/adverse effects/pharmacokinetics/therapeutic use
MH  - *Crohn Disease/drug therapy/immunology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunologic Tests
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC8451784
OTO - NOTNLM
OT  - Crohn's disease
OT  - E6011
OT  - fractalkine
OT  - leukocyte trafficking
EDAT- 2021/02/19 06:00
MHDA- 2022/02/03 06:00
PMCR- 2021/09/20
CRDT- 2021/02/18 08:39
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/06/23 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2021/02/19 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/02/18 08:39 [entrez]
PHST- 2021/09/20 00:00 [pmc-release]
AID - JGH15463 [pii]
AID - 10.1111/jgh.15463 [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2021 Aug;36(8):2180-2186. doi: 10.1111/jgh.15463. Epub 
      2021 Mar 31.