Randomized trial of granulocyte colony-stimulating factor for spinal cord injury
Authors: Koda Masao , Hanaoka Hideki , Fujii Yasuhisa , Hanawa Michiko , Kawasaki Yohei , Ozawa Yoshihito , Fujiwara Tadami , Furuya Takeo , Ijima Yasushi , Saito Junya , Kitamura Mitsuhiro , Miyamoto Takuya , Ohtori Seiji , Matsumoto Yukei , Abe Tetsuya , Takahashi Hiroshi , Watanabe Kei , Hirano Toru , Ohashi Masayuki , Shoji Hirokazu , Mizouchi Tatsuki , Kawahara Norio , Kawaguchi Masahito , Orita Yugo , Sasamoto Takeshi , Yoshioka Masahito , Fujii Masafumi , Yonezawa Katsutaka , Soma Daisuke , Taneichi Hiroshi , Takeuchi Daisaku , Inami Satoshi , Moridaira Hiroshi , Ueda Haruki , Asano Futoshi , Shibao Yosuke , Aita Ikuo , Takeuchi Yosuke , Mimura Masaya , Shimbo Jun , Someya Yukio , Ikenoue Sumio , Sameda Hiroaki , Takase Kan , Ikeda Yoshikazu , Nakajima Fumitake , Hashimoto Mitsuhiro , Hasue Fumio , Fujiyoshi Takayuki , Kamiya Koshiro , Watanabe Masahiko , Katoh Hiroyuki , Matsuyama Yukihiro , Hasegawa Tomohiko , Yoshida Go , Arima Hideyuki , Yamato Yu , Oe Shin , Togawa Daisuke , Kobayashi Sho , Akeda Koji , Kawamoto Eiji , Imai Hiroshi , Sakakibara Toshihiko , Sudo Akihiro , Ito Yasuo , Kikuchi Takeshi , Takigawa Tomoyuki , Morita Takuya , Tanaka Nobuhiro , Nakanishi Kazuyoshi , Kamei Naosuke , Kotaka Shinji , Baba Hideo , Okudaira Tsuyoshi , Konishi Hiroaki , Yamaguchi Takayuki , Ito Keigo , Katayama Yoshito , Matsumoto Taro , Matsumoto Tomohiro , Kanno Haruo , Aizawa Toshimi , Hashimoto Ko , Eto Toshimitsu , Sugaya Takehiro , Matsuda Michiharu , Fushimi Kazunari , Nozawa Satoshi , Iwai Chizuo , Taguchi Toshihiko , Kanchiku Tsukasa , Suzuki Hidenori , Nishida Norihiro , Funaba Masahiro , Sakai Takashi , Imajo Yasuaki , Yamazaki Masashi 
Published: January 2021

Abstract
Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. The present trial failed to show a significant effect of G-CSF in primary end point.