Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome

The pharmacokinetics and safety ot HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 ± 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 ± 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 ± 6.8 hours) and plasma concentration after infusion (30.7 ± 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponentlal function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 ± 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 ± 0.02 L/kg) were different ( p