Background and Aims

A sizable portion of patients with AIS, though treated within the recommended time windows for reperfusion therapies (RTs) still suffer from incomplete recanalization, or from recurring or downstream obstruction translating in unsatisfactory neurologic recovery. Glenzocimab, a novel antibody fragment targeting platelet GPVI, is tested to safely improve the efficacy of RTs.

Primary ACTIMIS study goal is to evaluate glenzocimab safety on top of RTs in AIS patients. The first study milestone was to complete the escalating dose phase and to choose a safe dose for the phase 2.

Methods

A multinational, randomized, double blind, placebo-controlled, single escalating dose study. All patients eligible to tPA (AIS onset ≤ 4.5hr), 50% of them also to thrombectomy received either placebo (n=12) or glenzocimab following a sequential escalating dose scheme, 125mg, 250mg, 500mg and 1000mg (n=12 per dose). The primary endpoint was the occurrence of symptomatic and non-symptomatic intracranial hemorrhages (ICHs), serious adverse events (SAEs), bleeding-related events (BREs) and deaths.

Results

Sixty patients were included. Of the 39 SAEs, 17 were ICHs, 1 symptomatic and 16 non-symptomatic ones. Of the 22 other SAEs, none was related to study drug, 17 recovered and 5 had a fatal outcome. Ten non-ICH BREs occurred, 2 of them were considered as SAEs. There was no dose-effect trend for any of the safety parameters.

Conclusions

Glenzocimab showed a favorable safety profile with an overall rate of 1.7% of symptomatic ICH, similar to that of i.v. thrombolysis in routine practice. The 1000mg dose was selected for phase 2.