BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children

Abstract

Purpose: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID.

Methods: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient's pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated.

Results: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates.

Conclusion: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID.

Trial registration: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.

Keywords: Children; Clinical trial; Efficacy; Intravenous immunoglobulin (IVIg); Pharmacokinetics; Primary immunodeficiency (diseases) (PID); Safety; Serious bacterial infections; Tolerability.

Conflict of interest statement

Gergely Kriván was coordinating investigator of the trial and has received research grants from Biotest AG. Michael Borte, Pere Soler-Palacin, Joseph A. Church, Ildiko Csurke, James B. Harris, Jay A. Lieberman, Isaac R. Melamed, James N. Moy, and Reka Simon were principal investigators of children recruiting active sites. Silke Aigner, Stephan Lentze, and Christiane Staiger are employees of the trial sponsor Biotest AG, Dreieich, Germany.

© 2022. The Author(s).

Figures

Fig. 1

Trough levels of total IgG (box plots) at steady state for BT595 and previous immunoglobulin by age group—PK trough set (N = 67). Css, concentration at steady state; IgG, immunoglobulin G, IQR, interquartile range (25 to 75% percentile); IVIg, immunoglobulin for intravenous administration; Min, minimum; Max, maximum; Q3W, 3-week schedule; Q4W, 4-week schedule. The cross symbol represents arithmetic mean and the dashed line represents the median value. The box represents the 1st and 3rd quartile (25th and 75th percentile). The whiskers represent the Min–Max range, or the 1.5-fold IQR in case of outliers (beyond the 1.5-fold IQR, shown as circles). Note: Steady-state concentrations of total IgG were assessed at local laboratories at baseline (steady state for reference therapy; after ≥ 3 months on the same IVIg reference treatment) and before infusion 7 or infusion 5 of BT595 (for the Q3W and Q4W schedules, respectively). Note: Horizontal dotted line refers to the targeted minimal trough level of 5 g/L