Pharmacokinetics of a New Intravenous Immunoglobulin (IVIg) 10% (KIg10) in Primary Immunodeficiency (PI) Patients

Introduction Intravenous immunoglobulin (IVIg) therapy is commonly used in the treatment of primary immunodeficiency (PI) disorders. This open-label, prospective, single-arm, multicenter phase III study in adult PI patients (KIG10_US3_PID01; NCT01581593) investigated efficacy, safety, and pharmacokinetics (PK) of a new 10% IVIg product (KIg10), given 200 to 800 mg/kg every 21 or 28 days for 48 weeks. Objective Primary PK endpoints included total IgG levels, IgG subclasses levels, selected specific antibody levels, and PK parameters of total and baseline-corrected IgG. Methods PK assessments were performed in 23 adult patients, and blood samples from them were taken for PK parameters’ analysis before and after the 5th infusion for the 28-day infusion schedule or the 7th infusion for the 21-day infusion schedule and at protocol prespecified time points. Results The estimated mean serum half-life (T1/2) for uncorrected total IgG was 24.5 days (587 h) and 37.3 days (896 h) for patients on 21- and 28-day schedule, respectively. The total serum IgG PK profiles were comparable between the two dosing schedules, with a numerically higher exposure for the 21-day schedule. All the mean values of IgG subclasses were maintained within the reference ranges following IV infusion of KIg10. All anti-tetanus toxoid antibody levels, mean values of anti-pneumococcal capsular polysaccharide antibodies, and mean levels of anti-Haemophilus influenzae type b antibodies were maintained above protective levels. Conclusion In study KIG10_US3_PID01, measured PK parameters for KIg10 in adult patients with PID were considered comparable with previously published data for other IVIg treatments. Table 1.Baseline-corrected PK ParameterKIg10 Dosing Schedule21-day (N = 5)28-day (N = 18)Cmax (mg/dL), mean (SD)1510 (12.1)1210 (33.8)T1/2 (hours), mean (SD)107 (45.5)158 (48.4)AUC0-t (day*mg/dL), mean (SD)8250 (20.0)8870 (34.7)Cmax = maximum observed concentration; T1/2 = terminal half-life; AUC0-t = area under the concentration-time curve from time 0 to time t of the last quantifiable concentration.