TY - JOUR
T1 - Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in patients with Crohn's disease
AU - Matsuoka, Katsuyoshi
AU - Naganuma, Makoto
AU - Hibi, Toshifumi
AU - Tsubouchi, Hirohito
AU - Oketani, Kiyoshi
AU - Katsurabara, Toshinori
AU - Hojo, Seiichiro
AU - Takenaka, Osamu
AU - Kawano, Tetsu
AU - Imai, Toshio
AU - Kanai, Takanori
N1 - Funding Information:
The authors would like to thank the following principal investigators for their contributions to the study: Satoshi Tanida, Nagoya City University, Aichi, Japan; Kazuya Kitamura, Kanazawa University Hospital, Ishikawa, Japan; Toshiyuki Matsui, Fukuoka University Chikushi Hospital, Fukuoka, Japan; Makoto Arai, Chiba University, Chiba, Japan; Mikihiro Fujiya, Asahikawa Medical University, Hokkaido, Japan; Noriyuki Horiki, Mie University Hospital, Mie, Japan; Hiroko Nebiki, Osaka City General Hospital, Osaka, Japan; Fukunori Kinjo, Urasoe General Hospital, Okinawa, Japan; Takako Miyazaki, Hyogo College of Medicine, Hyogo, Japan; Takayuki Matsumoto, Iwate Medical University, Iwate, Japan; Motohiro Esaki, Kyushu University, Fukuoka, Japan; Keiichi Mitsuyama, Kurume University Hospital, Fukuoka, Japan; Masayuki Saruta, The Jikei University School of Medicine, Tokyo, Japan; Akio Ido, Kagoshima University, Kagoshima, Japan; Kiyonori Kobayashi, Kitasato University East Hospital, Kanagawa, Japan; Hiroshi Nakase, Kyoto University Hospital, Kyoto, Japan; Bunei Iizuka, Tokyo Women's Medical University, Tokyo, Japan; Ken Kawakami, Osaka Medical College, Osaka, Japan; Tetsuji Takayama, Tokushima University, Tokushima, Japan; Shinji Tanaka, Hiroshima University Hospital, Hiroshima, Japan; Shingo Kato, Saitama Medical University, Saitama, Japan; The authors also thank Mikiko Kawakatsu of Eisai Co., Ltd., for writing support which was funded by EA Pharma Co., Ltd.
Publisher Copyright:
© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
PY - 2021/8
Y1 - 2021/8
N2 - 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 α 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.
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 α 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.
KW - Crohn's disease
KW - E6011
KW - fractalkine
KW - leukocyte trafficking
UR - http://www.scopus.com/inward/record.url?scp=85103969493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103969493&partnerID=8YFLogxK
U2 - 10.1111/jgh.15463
DO - 10.1111/jgh.15463
M3 - Article
C2 - 33599356
AN - SCOPUS:85103969493
SN - 0815-9319
VL - 36
SP - 2180
EP - 2186
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 8
ER -