A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barré Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS).
BACKGROUND
Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation.


OBJECTIVE
This clinical trial aims to evaluate the efficacy and safety of eculizumab, a humanized monoclonal antibody directed against complement component 5, for treatment of GBS.


METHODS
The Japanese Eculizumab Trial for GBS (JET-GBS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 33 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3-5) were randomized at a 2:1 ratio to receive either intravenous eculizumab (900 mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow-up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial.


RESULTS
Enrollment for the trial began in August 2015. This trial is still ongoing. All participants have been enrolled, and follow-up will be completed in October 2016.


CONCLUSIONS
This study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients.


BACKGROUND
UMIN Clinical Trials Registry UMIN 000018171; https:/upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function= brows&action=brows&type=summary&language=J&recptno=R000020978 (Archived by WebCite at http://www.webcitation.org/ 6lTiG8ltG). Clinical Trials.gov NCT02493725; https://clinicaltrials.gov/ct2/show/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL).
Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Nobuko
http://orcid.org/0000-0003-4838-3592
N
Yamaguchi
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Sonoko
http://orcid.org/0000-0002-8533-5664
S
Misawa
Department of Global Clinical Research, Chiba University Graduate School of Medicine, Chiba, Japan.
Yasunori
http://orcid.org/0000-0002-7189-5126
Y
Sato
Department of Global Clinical Research, Chiba University Graduate School of Medicine, Chiba, Japan.
Kengo
http://orcid.org/0000-0003-4529-9045
K
Nagashima
Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Kanako
http://orcid.org/0000-0002-1381-3241
K
Katayama
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Yukari
http://orcid.org/0000-0002-8531-2446
Y
Sekiguchi
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Yuta
http://orcid.org/0000-0003-2866-0169
Y
Iwai
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Hiroshi
http://orcid.org/0000-0002-0219-8482
H
Amino
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Tomoki
http://orcid.org/0000-0002-9575-9444
T
Suichi
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
Takanori
http://orcid.org/0000-0002-6490-3263
T
Yokota
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
Yoichiro
http://orcid.org/0000-0001-6158-9355
Y
Nishida
Department of Neurology, Kobe City Medical Centre General Hospital, Kobe, Japan.
Nobuo
http://orcid.org/0000-0001-7062-6306
N
Kohara
Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
Koichi
http://orcid.org/0000-0002-6492-4734
K
Hirata
Department of Neurology, Kitasato University School of Medicine, Kanagawa, Japan.
Kazutoshi
http://orcid.org/0000-0002-2051-977X
K
Nishiyama
Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Ichiro
http://orcid.org/0000-0002-1734-7997
I
Yabe
Division of Neurology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Ken-Ichi
http://orcid.org/0000-0002-8039-7233
KI
Kaida
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
Norihiro
http://orcid.org/0000-0002-0399-6590
N
Suzuki
Department of Clinical Neuroscience, Graduate School of Medical Sciences, Tokushima University, Tokushima, Japan.
Hiroyuki
http://orcid.org/0000-0002-5357-5081
H
Nodera
Department of Neurology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Shoji
http://orcid.org/0000-0001-5602-5686
S
Tsuji
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Haruki
http://orcid.org/0000-0002-4612-3183
H
Koike
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Jun-Ichi
http://orcid.org/0000-0001-5307-2671
JI
Kira
Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Hideki
http://orcid.org/0000-0003-0186-9296
H
Hanaoka
Department of Neurology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan.
Susumu
http://orcid.org/0000-0002-1584-8704
S
Kusunoki
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
Satoshi
http://orcid.org/0000-0002-4716-8578
S
Kuwabara
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Neurology, Kobe City Medical Centre General Hospital, Kobe, Japan.|Department of Neurology, Dokkyo Medical University, Tochigi, Japan.|Department of Neurology, Kitasato University School of Medicine, Kanagawa, Japan.|Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.|Division of Neurology, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.|Department of Neurology, Keio University School of Medicine, Tokyo, Japan.|Department of Clinical Neuroscience, Graduate School of Medical Sciences, Tokushima University, Tokushima, Japan.|Department of Neurology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.|Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Department of Neurology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan.
Guillain-Barré syndrome; antiganglioside antibody; clinical trial; complement activation; eculizumab