LB-005 Hemera 1 carboxyhemoglobin oxygendelivery for revascularization in acute stroke: a prospective, randomized phase 1 clinical trial

<h3>Background</h3> PP-007 is a PEGylated bovine carboxyhemoglobin gas transfer molecule with pleotropic cytoprotective effects, vasodilatation, plasma expansion and optimization of oxygen delivery. Rodent middle cerebral artery occlusion models have demonstrated that PP-007 increases blood flow in the collateral circulation and reduces final infarct volumes, supporting a potential role as neuroprotective agent in acute ischemic stroke. We aim to evaluate the safety and feasibility of PP-007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion (LVO). <h3>Methods</h3> HEMERA-1 was a multicenter, prospective, randomized, controlled phase 1 clinical trial. Anterior circulation LVO patients were assigned in a 3:1 ratio to receive either PP-007 (320mg/kg: 30 minutes bolus followed by 2-hour infusion) plus MT or MT alone within 24 hours after symptom onset. Other key inclusion criteria were baseline NIHSS ≥6, baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥5 and/or estimated core volumes ≤70mL with mismatch &gt;50mL on CT perfusion, pre-morbid modified Rankin Scale &lt;2, and ineligibility for intravenous thrombolysis. The primary endpoint comprised a comprehensive safety evaluation by a Data Monitoring Safety Board. <h3>Results</h3> A total of 17 patients were recruited. The mean ± SD age, baseline NIHSS, and ASPECTS were 74.8±12.7 years, 17.3±4.2, and 7.9±1.8, respectively. Twelve patients were randomized PP-007 plus MT, 1 was randomized but not treated, 4 patients were randomized to MT alone. Recanalization of the occluded vessel was achieved in all patients. Seven PP-007 patients in 2 centers had temporary elevation of Partial Prothrombin Time most likely artifactual without any clinical consequences. A transient systolic blood pressure increase (20-40 mmHg) during the bolus was observed in all PP-007 patients without any clinical consequences. There were no other safety concerns. <h3>Conclusion</h3> No significant safety concerns were identified for the adjunctive use of PP-007in patients undergoing MT (ClinicalTrials.gov NCT04677777). <h3>Disclosures</h3> <b>I. Linfante:</b> 2; C; Penumbra, Stryker, Q’Appel, Cerenovus. 3; C; Penumbra, Stryker, Q’Appel, Cerenovus. 4; C; Prolong Pharmaceuticals, InNeuroCo,Three Rivers, InNeuroFine, Deinde. <b>W. Clark:</b> None. <b>D. Houssen:</b> None. <b>R. Hanel:</b> None. <b>R. Reshi:</b> None. <b>G. Dabus:</b> 4; C; three rivers, InNeuroCo, synchron. <b>R. Jubin:</b> 5; C; Prolong Pharmaceuticals. <b>T. Nguyen:</b> None. <b>J. Grotta:</b> None. <b>R. Wicks:</b> None. <b>M. Pervez:</b> None. <b>M. Cipolla:</b> None. <b>D. Liebeskind:</b> None. <b>R. Nogueira:</b> None.