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Stroke. 2013 Oct;44(10):2681-7. doi: 10.1161/STROKEAHA.113.001531. Epub 2013 Aug 20.

Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial.

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From the Department of Neurology, University of Münster, Münster, Germany (E.B.R.); Department of Neurology, University of Leuven, Leuven, Belgium (V.T.); Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Department of Clinical Sciences, Section of Neurology, Lund University, Lund, Sweden (B.N.); Department of Neurology, University of Barcelona, Barcelona, Spain (A.C.); Department of Neurology, Nervenklinik Wagner-Jauregg, Linz, Austria (F.A.); Department of Neurology, Kreiskrankenhaus Siegen, Siegen, Germany (M.G.); Department of Neurology, University of California, Los Angeles (J.S.); Clinical Research Department, SYGNIS Bioscience GmbH, Heidelberg, Germany (R.L., A.S., F.R., G.V., G.C.); Center for Stroke Research, Charité, Berlin, Germany (J.B.F.); Department of Neurology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany (W.-R.S.); Department of Neurology, UMass Memorial Medical Center, Worcester, MA (M.F.); Department of Neurology, Medical Faculty Hospital Nitra, Nitra, Slovakia (M.B.); Department of Neurology, University Ostrava, Ostrava, Czech Republic (D.S.); Department of Neurology, Allgemeines Krankenhaus Linz, Linz, Austria (F.G.); Department of Neurology, Hospital Universitario Dr Josep Trueta de Girona, Girona, Spain (J.S.L.); Department of Neurology, University of Heidelberg, Heidelberg, Germany (R.V.); Department of Neurology, University of Erlangen, Erlangen, Germany (S.S., R.K., M.K.); and Department of Neurologie, Klinikum Altenburger Land GmbH, Altenburg, Germany (J.B.).



Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients.


G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging).


G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1.


G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers.

CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00927836.


G-CSF; MRI; clinical trial; hematopoietic growth factor; leukocytes; phase II; stroke

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