Objective:

Testing RNS60 as a new adjunctive cytoprotective therapy for acute ischemic stroke.

Background:

RNS60 is an experimental cytoprotective drug that showed significant therapeutic promise in rodent and primate models of ischemic stroke. RESCUE aimed to test adjunctive treatment with RNS60 in subjects with large vessel occlusion and acute ischemic stroke undergoing endovascular thrombectomy.

Design/Methods:

The multicenter, placebo-controlled, double-blind, Phase 2 study enrolled 82 participants, randomized for age, NIHSS, and ASPECTS to a 48-hour infusion with RNS60 0.5 mL/kg/h, RNS60 1 mL/kg/h, or placebo 1 mL/kg/h (1:1:1). 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, 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 and 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 had a 50% reduced infarct growth at 48 hours post-EVT (p<.05). On Day 90, RNS60 1 mL/kg/h demonstrated i) a 16% higher number of subjects with mRS 0-2 (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 at each pre-specified time point. 

Conclusions:

Adjunct treatment with RNS60 was generally safe and well tolerated, significantly reduced infarct growth, and demonstrated numerical improvement in all efficacy outcomes compared to placebo. Although not all differences are statistically significant in the context of limited power, these differences and odds ratios reflect a large, clinically meaningful difference. A Phase 3 study is in development.