Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody):: An open-label, dose escalation study in patients hospitalized for acute stroke

Background and Purpose: To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. Methods: An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. Results: The pharmacokinetic target levels (enlimomab serum levels of greater than or equal to 10 mu g/ml) were consistently achieved in all patients receiving dose regimens III and IV. Nonserious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. Conclusions: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.