Abstract / Summary
The 10% intravenous immunoglobulin (IVIG) BT595 was evaluated in an open-label, prospective, multicenter clinical trial (Trial 991; NCT02810444) to characterize IgG subclass pharmacokinetics as replacement therapy in patients with primary immunodeficiency (PID). Patients received BT595 at either a 3-week (Q3W) or 4-week (Q4W) dosing interval for approximately 12 months. Secondary endpoints included steady state trough concentrations and pharmacokinetic parameters of IgG subclasses 1-4 and total IgG. IgG subclass trough concentrations were assessed at baseline and at steady state prior to the 7th infusion (Q3W) or 5th infusion (Q4W). Pharmacokinetic parameters at steady state were determined in patients aged ≥6 years using serum samples collected predose and up to 28 days post infusion. At steady state, trough concentrations of total IgG and all IgG subclasses were comparable between BT595 and patients' previous IVIG therapy, indicating preservation of systemic IgG exposure following treatment switch. IgG subclass trough concentrations were stable across dosing regimens and age categories, with a proportional distribution closely matching physiological IgG composition. IgG1 and IgG2 accounted for the majority of total IgG, whereas IgG3 and IgG4 contributed smaller fractions, consistent with endogenous IgG and published IVIG data. Pharmacokinetic profiles of all IgG subclasses were consistent with those reported for licensed IVIG products. Maximum concentrations occurred rapidly after infusion, and systemic exposure was robust under both dosing regimens. Mean concentrations and Cmax values were higher with Q3W dosing, while exposure over the dosing interval (AUCtau) was lower compared with Q4W dosing due to the shorter interval. Estimated half-life values were within or above ranges reported for other IVIG products, with numerically prolonged persistence of IgG2 and IgG4 under Q4W dosing. Overall, BT595 provides sustained IgG subclass exposure at steady state, supporting its suitability as IVIG replacement therapy in PID under both Q3W and Q4W regimens.