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, pharmacok inetics 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 receiv ed one of four fixed dose regimens of enlimomab. A loading dose of enl imomab administered within 24 h of the onset of stroke symptoms was fo llowed by four daily maintenance doses; total doses ranged from 140 to 480 mg. Results: The pharmacokinetic target levels (enlimomab serum l evels of greater than or equal to 10 mu g/ml) were consistently achiev ed in all patients receiving dose regimens III and IV. Nonserious adve rse 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 card iac 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 recov ered. The overall mortality in the study was 15.6% and the 30-day mort ality was 12.5%. There was no increase in the frequency of adverse eve nts with increasing doses of enlimomab. Conclusions: Doses of enlimoma b between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic str oke 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.