CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage Trial in Singapore (S-CATCH): A Phase 2b, Randomized, Double-blind, Placebo-Controlled Trial.

BACKGROUND

Subsequent to an intracerebral hemorrhage (ICH), a cascade of neuroinflammatory response drives the process of secondary brain injury. At present, no anti-inflammatory nor neuroprotective pharmacological interventions have been demonstrated to improve functional outcome after ICH. This Phase 2b study was designed to establish the safety and feasibility of CN-105, a neuroprotective and anti-inflammatory pentapeptide designed from the receptor binding region of apolipoprotein E, in patients with acute primary supratentorial ICH.

METHODS

The Singapore CN-105 in Participants with Acute Supratentorial ICH Trial (S-CATCH, NCT03711903) was a randomized, double-blind, placebo-controlled trial involving 60 patients (30 CN-105, 30 placebo) treated within 12 h of symptom onset. Safety was assessed through adverse events (AEs) and serious AEs (SAEs), while efficacy was evaluated using functional outcome measures, including the modified Rankin Scale (mRS) at 90 days.

RESULTS

CN-105 was safe and well tolerated in patients with acute ICH, with no significant differences in incidence of SAEs between groups (30% SAEs in placebo vs. 26.7% in CN-105). Notably, fewer patients treated with CN-105 group experienced in-hospital neurological deterioration (0 vs. 10% in placebo). While treatment was not associated with a statistically significant improvement in 90-day mRS, higher proportion of patients treated with CN-105 achieved favorable mRS scores (≤ 3) compared with those in the placebo group (77.8 vs. 66.7%; p = 0.35).

CONCLUSIONS

This Phase 2b trial confirmed the safety and feasibility of CN-105 administration in the acute setting of ICH. Although no statistically significant improvements in neurological outcomes were found, the observed trends warrant further investigation. Future Phase 3 trials should focus on refining patient selection and assessing the therapeutic efficacy of CN-105 in more targeted subgroups such as those with medium-sized subcortical ICH. Trial registration NCT03711903, https://clinicaltrials.gov/ https://clinicaltrials.gov/study/NCT03711903?term=NCT03711903&rank=1 . Registered 16 October 2018.