PMID- 28681650
OWN - NLM
STAT- MEDLINE
DCOM- 20180705
LR  - 20191210
IS  - 1439-7609 (Electronic)
IS  - 1439-7595 (Linking)
VI  - 28
IP  - 1
DP  - 2018 Jan
TI  - Safety, pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal 
      antibody, in a first-in-patient phase 1/2 study on rheumatoid arthritis.
PG  - 58-65
LID - 10.1080/14397595.2017.1337056 [doi]
AB  - OBJECTIVE: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and 
      adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We 
      conducted the first phase 1/2, open-label, multiple ascending dose study of 
      E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis 
      (RA) patients (clinicaltrial.gov identifier: NCT02196558). METHODS: Active RA 
      patients with an inadequate response or intolerance to methotrexate or tumor 
      necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter 
      every 2 weeks for 12 weeks. RESULTS: Twelve, 15, and 10 subjects were enrolled in 
      the 100, 200, and 400 mg cohorts, respectively. No severe adverse events (AEs) or 
      deaths occurred, and no major differences were observed in the incidence or 
      severity of AEs across the cohorts. Serum E6011 concentrations increased dose 
      dependently. American College of Rheumatology (ACR) 20, 50, and 70 responses at 
      week 12 were 75.0%, 33.3%, and 8.3% in the 100 mg cohort; 66.7%, 20.0%, and 13.3% 
      in the 200 mg cohort; and 60.0%, 30.0%, and 20.0% in the 400 mg cohort, 
      respectively. CONCLUSIONS: E6011 appeared to be safe and well tolerated in RA 
      patients during this 12-week treatment period, suggesting that E6011 has an 
      effective clinical response in active RA patients.
FAU - Tanaka, Yoshiya
AU  - Tanaka Y
AD  - a First Department of Internal Medicine , University of Occupational and 
      Environmental Health , Kitakyushu , Japan.
FAU - Takeuchi, Tsutomu
AU  - Takeuchi T
AD  - b Division of Rheumatology, Department of Internal Medicine , Keio University 
      School of Medicine , Tokyo , Japan.
FAU - Umehara, Hisanori
AU  - Umehara H
AD  - c Division of Rheumatology and Immunology , Nagahama City Hospital , Shiga , 
      Japan.
FAU - Nanki, Toshihiro
AU  - Nanki T
AD  - d Division of Rheumatology, Department of Internal Medicine , Toho University 
      School of Medicine , Tokyo , Japan.
FAU - Yasuda, Nobuyuki
AU  - Yasuda N
AD  - e KAN Research Institute, Inc. , Kobe , Japan.
FAU - Tago, Fumitoshi
AU  - Tago F
AD  - f Eisai Co., Ltd. , Tokyo , Japan.
FAU - Kawakubo, Makoto
AU  - Kawakubo M
AD  - f Eisai Co., Ltd. , Tokyo , Japan.
FAU - Kitahara, Yasumi
AU  - Kitahara Y
AD  - f Eisai Co., Ltd. , Tokyo , Japan.
FAU - Hojo, Seiichiro
AU  - Hojo S
AD  - f Eisai Co., Ltd. , Tokyo , Japan.
FAU - Kawano, Tetsu
AU  - Kawano T
AD  - e KAN Research Institute, Inc. , Kobe , Japan.
FAU - Imai, Toshio
AU  - Imai T
AD  - e KAN Research Institute, Inc. , Kobe , Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02196558
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170706
PL  - England
TA  - Mod Rheumatol
JT  - Modern rheumatology
JID - 100959226
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Chemokine CX3CL1)
RN  - G8NT4Q571B (quetmolimab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/*adverse effects/immunology/pharmacokinetics/therapeutic 
      use
MH  - Antibodies, Monoclonal, Humanized/*adverse 
      effects/immunology/pharmacokinetics/therapeutic use
MH  - Antirheumatic Agents/*adverse effects/immunology/pharmacokinetics/therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Chemokine CX3CL1/*immunology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - E6011
OT  - first-in-patient
OT  - fractalkine
OT  - monoclonal antibody
OT  - rheumatoid arthritis
EDAT- 2017/07/07 06:00
MHDA- 2018/07/06 06:00
CRDT- 2017/07/07 06:00
PHST- 2017/07/07 06:00 [pubmed]
PHST- 2018/07/06 06:00 [medline]
PHST- 2017/07/07 06:00 [entrez]
AID - 10.1080/14397595.2017.1337056 [doi]
PST - ppublish
SO  - Mod Rheumatol. 2018 Jan;28(1):58-65. doi: 10.1080/14397595.2017.1337056. Epub 
      2017 Jul 6.