Abstract Body:
Objective and Background: Developing cerebroprotective therapies for stroke remains an unmet need despite improvements in early reperfusion. RNS60 is an experimental cerebroprotective drug that showed significant promise in rodent and primate models of ischemic stroke. RESCUE is a proof-of-concept trial to test adjunctive treatment with RNS60 in subjects with large vessel occlusion and acute ischemic stroke undergoing endovascular thrombectomy (EVT).

Method: The multicenter, placebo-controlled, double-blind, Phase 2 study enrolled 82 participants, randomized 1:1:1 for age, NIHSS, and ASPECTS to a 48-hour infusion (RNS60 0.5 mL/kg/h, RNS60 1 mL/kg/h RNS60, or placebo 1 mL/kg/h). Participants were followed for 90 days with safety as primary objective. The primary efficacy endpoints included dichotomized day-90 mRS, infarct volume at 48 hours, BI and EQ-5D-5L on day 90, and NIHSS at multiple time points.

Results: The study met its primary endpoint of safety and mortality, with similar rates of SAEs in all arms and numerically lower numbers of deaths in the RNS60 groups compared to placebo. The RNS60 1 mL/kg/h group performed numerically better than placebo in all prespecified endpoints and reduced infarct growth at 48 hours post-EVT by 50% (p<.05). On Day 90, RNS60 1 mL/kg/h demonstrated i) a 16% higher number of subjects having mRS 0-2 compared to placebo (22% predicted probability, OR 3.7, p=.36), ii) a higher number of subjects with BI ≥ 95 (71% on RNS60 1 mL/kg/h vs. 43% on placebo; OR 5.8, p=.13), iii) improved EQ-5D-5L index score (0.74 ± 0.13 on RNS60 1 mL/kg/h vs. 0.58 ± 0.13 on placebo; p=.09) and iv) improved NIHSS score (absolute value and change from baseline) at each pre-specified time point. Although not all are statistically significant, these differences and odds ratios reflect a large, clinically meaningful difference.

Conclusion: Adjunct treatment with RNS60 was generally safe and well tolerated, reduced infarct growth, and demonstrated numerical improvement in all efficacy outcomes. In the context of limited power, point estimates raise the possibility of benefit with respect to all efficacy endpoints tested. A Phase 3 study is in development.