Intravenous Odatroltide for Acute Ischemic Stroke Within 24 Hours of Onset: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

A-Ching Chao,1,2 Tsong-Hai Lee,3 Luther C Pettigrew,4 Yousef Hannawi,5 Hung-Yu Huang,6 Nai-Fang Chi,7,8 Lung Chan,9,10 Po-Lin Chen,11 Thomas Devlin12,13 1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 2College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, KY, USA; 5Division of Cerebrovascular Diseases and Neurocritical Care, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 7School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 8Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; 9Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 10Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 11Division of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan; 12CHI Memorial Neuroscience Institute, Chattanooga, TN, USA; 13Department of Neurology, Morehouse School of Medicine, Atlanta, GA, USACorrespondence: Thomas Devlin, Chattanooga Center for Neurological Research, 725 Glenwood Drive, Suite 880-A, Chattanooga, TN, 37404, USA, Email devlinmdphd@gmail.comPurpose: Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic stroke within 24 hours of onset.Patients and Methods: Patients with National Institutes of Health Stroke Scale (NIHSS 4– 30) who were untreated with intravenous thrombolysis or endovascular thrombectomy were randomized (2:1) to receive a single dose of odatroltide (0.025 mg/kg) or placebo within 24 hours of stroke symptom onset. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) occurrence within 36 hours.Results: Twenty-four patients were enrolled and randomized; of these 16 and 8 received intravenous odatroltide infusion and placebo, respectively. sICH did not occur in both groups, and other safety measures were comparable between the groups. The rate of excellent functional outcome (modified Rankin Scale score, 0– 1, at 90 days) was 21% and 14% in the odatroltide and placebo groups, respectively. Furthermore, 47% and 14% of patients in the odatroltide and placebo groups, respectively, showed major neurological improvement (NIHSS improvement ≥ 4 points from baseline to 30 days). Among the 9 odatroltide-treated patients with baseline NIHSS ≥ 6, 78% showed major neurological improvement.Conclusion: Compared with placebo, treatment with intravenous odatroltide within 24 hours following onset of ischemic stroke appears to be safe and may be associated with better neurological and functional outcomes. However, the efficacy and safety of odatroltide requires further confirmation in the next phase of clinical trials.Clinical Trial Registration: Clinicaltrials.gov identifier: NCT04091945.Keywords: LT3001, ischemic stroke, rtPA