Safety, pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody, in a first-in-patient phase 1/2 study on rheumatoid arthritis

Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Yasumi Kitahara, Seiichiro Hojo, Tetsu Kawano, Toshio Imai

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalModern Rheumatology
DOIs
Publication statusAccepted/In press - 2017 Jun 27

Fingerprint

Rheumatoid Arthritis
Pharmacokinetics
Monoclonal Antibodies
Safety
CX3C Chemokines
Chemokine CX3CL1
Chemokine Receptors
Chemotaxis
Chemokines
Methotrexate
Tumor Necrosis Factor-alpha
Incidence
Serum
Therapeutics

Keywords

  • E6011
  • first-in-patient
  • fractalkine
  • monoclonal antibody
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

Safety, pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody, in a first-in-patient phase 1/2 study on rheumatoid arthritis. / Tanaka, Yoshiya; Takeuchi, Tsutomu; Umehara, Hisanori; Nanki, Toshihiro; Yasuda, Nobuyuki; Tago, Fumitoshi; Kawakubo, Makoto; Kitahara, Yasumi; Hojo, Seiichiro; Kawano, Tetsu; Imai, Toshio.

In: Modern Rheumatology, 27.06.2017, p. 1-8.

Research output: Contribution to journalArticle

Tanaka, Yoshiya ; Takeuchi, Tsutomu ; Umehara, Hisanori ; Nanki, Toshihiro ; Yasuda, Nobuyuki ; Tago, Fumitoshi ; Kawakubo, Makoto ; Kitahara, Yasumi ; Hojo, Seiichiro ; Kawano, Tetsu ; Imai, Toshio. / Safety, pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody, in a first-in-patient phase 1/2 study on rheumatoid arthritis. In: Modern Rheumatology. 2017 ; pp. 1-8.
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abstract = "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.",
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AU - Takeuchi, Tsutomu

AU - Umehara, Hisanori

AU - Nanki, Toshihiro

AU - Yasuda, Nobuyuki

AU - Tago, Fumitoshi

AU - Kawakubo, Makoto

AU - Kitahara, Yasumi

AU - Hojo, Seiichiro

AU - Kawano, Tetsu

AU - Imai, Toshio

PY - 2017/6/27

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N2 - 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.

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.

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