Phase I study evaluating the safety and pharmacokinetics of MDX-1303, a fully human monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers.

MDX-1303 (Valortim) is a fully human monoclonal antibody (hMAb) with a high affinity for Bacillus anthracis protective antigen (PA). MDX-1303 binds to PA and interferes with the activity of the anthrax toxin; it was selected based on its superior functional activity in the toxin neutralization activity (TNA) assay. MDX-1303 has demonstrated efficacy in the postexposure and therapeutic settings in New Zealand White rabbits, cynomolgus monkeys, and African green monkeys. This phase I study sought to characterize the safety, tolerability, immunogenicity, and pharmacokinetics (PK)/pharmacodynamics (PD) of MDX-1303 in healthy human subjects. Cohorts of 3 to 10 subjects were administered MDX-1303 as either a single intravenous (i.v.) dose at dose levels of 0.3, 1, 3, 10, and 20 mg/kg of body weight or as a single intramuscular (i.m.) dose at 100 mg. Forty-six subjects were enrolled, and 16 (35%) of these subjects experienced one or more grade 1 adverse events considered to be related to treatment with MDX-1303. There were no grade 2 to 4 adverse events or serious adverse events (SAEs) considered to be related to treatment. The mean half-life of MDX-1303 ranged from 22 to 33 days across the i.v. administration cohorts and was approximately 32 days following i.m. administration. Systemic exposure following 100-mg i.m. administration was within the range of exposure following 1-mg/kg i.v. administration with a relative bioavailability of approximately 65%. MDX-1303 was generally well tolerated, and no anti-MDX-1303 antibodies were detected following a single dose.