Mikhail A. Rojavin, United States of America
CSL Behring LLC Clinical Research and DevelopmentPresenter of 3 Presentations
POPULATION PHARMACOKINETIC ANALYSIS OF IGPRO10 IN JAPANESE PATIENTS WITH PRIMARY IMMUNODEFICIENCY
Abstract
Background and Aims
We aimed to characterize the pharmacokinetics (PK) of serum immunoglobulin G (IgG) following 3- or 4-weekly administration of IgPro10 (Privigen®, CSL Behring) in Japanese patients with primary immunodeficiencies, and compare with non-Japanese patients. A previously-developed population PK (PPK) model (Landersdorfer CB et al., Postgrad Med 2013;125:53‒61) was validated, and predicted parameters compared with clinical study results.
Methods
The previously-developed PPK model, containing IgG concentration data from 5 non-Japanese studies, was supplemented with data from 3 Japanese studies (IgPro10 or IgPro20 [Hizentra®, CSL Behring]). The model was externally validated by simulating IgG concentration-time profiles in Japanese patients to predict serum IgG PK characteristics and compare with observed Japanese PK data in Study IgPro10_3004 (EudraCT: 2016-001631-12).
Results
The analysis included 4,502 serum IgG concentration values (34 Japanese/168 non-Japanese patients). PPK estimates from the current analysis were consistent with the previously-published PPK model (including clearance [%inter-individual variability, IIV], 0.139 [24%] vs 0.142 L/day; central volume, 4.01 [92.1%] vs 3.94 L, respectively), with similar bootstrap mean and 95% confidence intervals (CI). Prediction-corrected visual predictive checks confirmed a good description of data for SCIG and IVIG. PK parameters were equivalent between Japanese/non-Japanese patients. Simulated and observed area under concentration-time curve, and maximum and minimum serum IgG concentrations were similar (Figure), with 90% CI overlapping between simulated and observed values.
Conclusions
PK parameter estimates of serum IgG were similar between Japanese and non-Japanese patients. The PPK model, updated with Japanese data, could accurately predict both individual and population serum IgG concentration-time profiles following 3-weekly and 4-weekly IgPro10.
SAFETY AND TOLERABILITY OF IGPRO10 (PRIVIGEN®) IN JAPANESE PATIENTS WITH PRIMARY IMMUNODEFICIENCY: DATA FROM A PHASE 3 STUDY
Abstract
Background and Aims
Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiency (PID). Intravenous (IVIG) requires less frequent infusions and is beneficial for highly symptomatic patients, due to an immediate rise in serum IgG concentration post-infusion. IVIG is favorable for elderly and patients with aversion to self-administration. This study assessed the safety of Privigen® (IgPro10, CSL Behring, King of Prussia, PA, USA) in Japanese PID patients.
Methods
This was a prospective, Phase 3, open-label, single-arm study. Privigen® was administered at pre-study doses of 138–556 mg/kg body weight per dosing cycle (3- or 4-weekly) for up to 4 months including a 12-week wash-in/wash-out period. Frequency and intensity of adverse events (AEs), relationship to study drug and AE rate per infusion (AERI) were assessed.
Results
Ten patients completed the study. The median (range) total duration of exposure was 16.14 (4.1–16.3) weeks. A total of 19 AEs, most of which mild (45.5%), were reported in 8 patients, giving an AERI of 0.442. One AE was deemed related to Privigen® treatment (infusion site discomfort, resolved). Three patients experienced temporally associated AEs (within 72 h post-infusion). No serious AEs or deaths were reported. Most patients (90%) tolerated flow rates of ≥8 mg/kg/min, of which 5 (50%) tolerated 12 mg/kg/min. This translated into a 3-fold decrease in mean (SD) infusion time, from 173.4 (53.65) min for the first to 58.5 (14.24) min during the fourth infusion.
Conclusions
Privigen® was well tolerated at flow rates of up to 12 mg/kg/min.
PHARMACOKINETIC PROPERTIES OF IGPRO10 IN JAPANESE PATIENTS WITH PRIMARY IMMUNODEFICIENCY
Abstract
Background and Aims
The pharmacokinetic (PK) properties of IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, USA), a 10% liquid intravenous immunoglobulin (IVIG), are well-established in non-Japanese patients with primary immunodeficiency (PID). This study evaluated PK parameters of IgPro10 in Japanese patients with PID.
Methods
This was a prospective, Phase 3, open-label, single-arm study of IgPro10 in Japanese patients with PID. IgPro10 (138–554 mg/kg body weight, as per patient’s last steady-state dose) was administered in 3- or 4-weekly dosing regimens for up to 4 months. Serum samples for PK analysis were collected during the last IgPro10 dosing cycle (beginning from Week 13). PK parameters including area under the concentration-time curve from time point zero to the last quantifiable time point (AUC0–last), dose-adjusted AUC0–last (dAUC), lowest/highest observed immunoglobulin G levels (Cmin/Cmax), time to reach Cmax (Tmax), and total clearance (CL) were analyzed for both dosing regimens.
Results
Ten patients were included in this analysis (3-weekly/4-weekly: n=2/n=8); the small number of patients in the 3-weekly regimen limits the interpretation. Cmax was observed approximately 1 h after the start of the infusion in both treatment groups. Mean (SD [not applicable for 3-weekly infusion parameters]) PK parameters were: Cmax, 16.60 and 14.20 (5.53) g/L; Cmin, 10.60 and 8.53 (3.89) g/L; AUC0–last, 5971 and 6591 (2633) g*h/L; dAUC, 0.41 and 0.46 (0.19) g*h/L; CL, 2.53 and 2.53 (0.99) mL/h and median Tmax was 1.19 and 1.14 h, for 3-weekly/4-weekly dosing regimens, respectively.
Conclusions
PK parameters of IgPro10 in Japanese patients were similar between 3- and 4-weekly dosing regimens.