Abstract Number ‐ 8: HEMERA 1 CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke: Phase 1 Clinical Trial

Abstract

Introduction Despitehigh rates ofrecanalizationafter mechanical thrombectomy(MT),only 33–71% of patients achieve functional independence at 90 days.Experimental ischemia hashighlightedthe complexity of several pathophysiological events occurring at the level of the neurovascular unit and has revealed potential targets for neuroprotection. Apossible target is to increasebloodflow in the collateral circulationwhile delivering high levels of oxygen in the ischemic area.Hemoglobin based oxygen carriers (HBOC) as a transfusion media that can treat ischemic tissue have been investigatedfor a decade. More recently, a polyethylene glycol modifiedHBOCin the carboxy state (PP‐007)increases blood flow in the collateral circulationinrat modelsof middle cerebral artery occlusion (MCAO).PP‐007 may deliver more oxygen than Hb contained in RBCs because of increased diffusional surface area in plasma, and by facilitation of oxygen transport from RBC to endothelium.In addition,dilation ofcollateral circulationby diffusion of CO mayslow down infarct expansion andimprove the efficacy of reperfusion. Methods HEMERA 1 is a phase 1 safety clinical trialof PP‐007 in patient with acute ischemic strokewith LVO (ClinicalTrials.gov NCT04677777). Inclusion criteria are patients with Intracranial ICA and/or MCA‐M1 or M2 occlusion,baseline NIHSS ≥ 6, Baseline ASPECTS score ≥ 5 on NCCT and/or Core Volumes 50mL on CT perfusion (CTP), time fromlast seen well to start ofPP‐007infusion ≤ 24 hours,pre‐MorbidmRS< 2, and ineligibility for intravenous thrombolysis. The trial plans to enroll approximately 16–20 subjectswith3:1 randomizationtoPP‐007 (320 mg/kg with 30 min bolus + 2‐hour infusion) plus MT versus MT alone. Results Tenpatients have been enrolled so far.Mean age was 76.1 (STD±11.6), ASPECT score = 7.8 (±1.8), NIHSS at baseline = 17.3 (±5.6),TICI 2b or c in 7, TICI 3 in 3. Seven patients were randomized PP‐007 and received the complete infusion. Two patients were randomized to standard of care (MT only) and1was randomized to PP‐007 but not treated.Three patients had elevation of Partial Prothrombin Time (PTT) after the PP‐007 infusion that however had no clinical consequences. Conclusions HEMERA 1 isphase 1 clinical trialcurrently enrolling patients.No safety concerns were identified so far.