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

Abstract

Purpose

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

Abbreviations

AE, Adverse events; AIS, Acute ischemic stroke; ASPECTS, Alberta Stroke Program Early CT Score; CI, Confidence intervals; CT, Computed tomography; MRI, Magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale; RR, Relative risk; SAE, Serious adverse event; SD, Standard deviation; TEAE, Treatment-emergent adverse events.

Data Sharing Statement

The dataset used and/or analyzed in this study will be available through de-identification from the corresponding author upon reasonable request within one week.

Ethics Approval and Informed Consent

The ethics committee of all participating centers approved the study protocol.

Acknowledgments

We are thankful to the patients and their families for their participation, trust, and partnership. Furthermore, we are grateful to Dr. Pooja Khatri for editing the manuscript. The abstract of this paper was presented at the 2021 World Stroke Organization Congress as a poster presentation with the number: WSC21-570. The poster’s abstract was published in “WSO Congress supplement” in the International Journal of Stroke 2021, Vol. 16(2S) 3–170: Hyperlink with DOI 10.1177/17474930211041949.

Author Contributions

All authors contributed to the study conception and design, execution, data collection, analysis, and interpretation. Each version of the submitted article was drafted, revised, and critically reviewed by all authors. All authors approved the article and any subsequent revisions for submission, and they are responsible for the entire content of this article.

Disclosure

Dr Luther Pettigrew reports grants from Lumosa Therapeutics Co., Ltd., during the conduct of the study; grants from NIH/NINDS, United States, outside the submitted work. Dr Yousef Hannawi reports grants from Lumosa Therapeutics Co, Ltd, during the conduct of the study. Dr Thomas Devlin reports personal fees from Medtronic, Viz.ai, NeuraSignal, and Neuro Trauma Sciences, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was supported by Lumosa Therapeutics Co., Ltd.