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)

Abstract

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.

Clinicaltrial: 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://ichgcp.net/clinical-trials-registry/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL).

Keywords: Guillain-Barré syndrome; antiganglioside antibody; clinical trial; complement activation; eculizumab.

Conflict of interest statement

The investigational product is provided by US-based Alexion Pharmaceuticals Inc under the Global Investigator-Sponsored Research Program. The interest profile of this trial is to be reviewed and approved by the conflict of interest committees of the participating sites, all in accordance with the applicable regulatory requirements and guidelines, and potential conflicts addressed through conflict of interest management and integrity assurance efforts.

©Nobuko Yamaguchi, Sonoko Misawa, Yasunori Sato, Kengo Nagashima, Kanako Katayama, Yukari Sekiguchi, Yuta Iwai, Hiroshi Amino, Tomoki Suichi, Takanori Yokota, Yoichiro Nishida, Nobuo Kohara, Koichi Hirata, Kazutoshi Nishiyama, Ichiro Yabe, Ken-Ichi Kaida, Norihiro Suzuki, Hiroyuki Nodera, Shoji Tsuji, Haruki Koike, Jun-Ichi Kira, Hideki Hanaoka, Susumu Kusunoki, Satoshi Kuwabara, JET-GBS Group. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.11.2016.

Figures

Figure 1

Schematic depiction of the trial design. The study is composed of 3 periods: the screening period, investigational product (IP) administration period (4 weeks), and post-IP period follow-up (20 weeks).