CN-105 in Participants with Acute SupraTentorial IntraCerebral Hemorrhage (CATCH) Trial

Abstract

AbstractBackgroundEndogenous apoliloprotein E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apolipoprotein E-mimetic peptides can effectively penetrate the brain and down-regulate acute inflammation. CN-105 is a novel apolipoprotein E-mimetic pentapeptide with excellent preclinical evidence as an acute intracerebral hemorrhage (ICH) therapeutic. The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state, multi-center, open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH.MethodsEligible patients were age 30-80 years, had confirmed primary supratentorial ICH, and able to intiate CN-105 administration (1.0 mg/kg every 6 hours for 72 hours) within 12 hours of symptom onset. A priori defined safety endpoints, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes were analyzed. For comparisons, CATCH participants were matched 1:1 with a contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on Days 0, 1, 2, and 5 and ordinal modified Rankin Score at 30 days after ICH were compared.ResultsIn 39 participants enrolled across six study sites in the United States, adverse events occurred at expected rate without increase in hematoma expansion or neurological deterioration or significant serum accumulation. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31–5.51) for lower 30-day mRS, after adjustment for ICH Score, sex, and race/ethnicity, compared to matched contemporary cohort.ConclusionCN-105 administration represents an excellent translational candidate as an actue ICH therapeutic due to its safety, dosing feasibility, favorable pharmacokinetics, and evidence of improved neurological recovery.