Wasserman Richard L, Melamed Isaac R, Stein Mark R, Jolles Stephen, Norton Miranda, Moy James N
Allergy Partners of North Texas Research, Dallas, TX, USA.
IMMUNOe International Research Centers, Centennial, CO, USA.
J Clin Immunol. 2017 Apr;37(3):301-310. doi: 10.1007/s10875-017-0383-9. Epub 2017 Mar 18.
This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs).
Eligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only.
The primary objective, to demonstrate the bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval, was met based on the Gammaplex 10%/Gammaplex 5% ratio of area under the concentration versus time curve (AUC) values. Throughout the study, total immunoglobulin G trough levels were well maintained, with total values generally ≥600 mg/dL (minimum level for study inclusion). At the dosing schedules and infusion rates used in this study, safety and tolerability were comparable and acceptable in adult and pediatric PID subjects treated with Gammaplex 10% and 5%.
In this study, the first direct comparison of 5% IVIG and 10% IVIG products in PID subjects, the pharmacokinetic analysis demonstrated bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval. The Gammaplex 10% formulation was safe and well tolerated in pediatric and adult PID subjects. Based on the results from this bridging study in PID subjects, Gammaplex 10% could be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated efficacy and tolerability in patients with PID and idiopathic thrombocytopenic purpura.
本3期、多中心、开放标签、随机、两周期、交叉生物等效性试验评估了静脉注射免疫球蛋白（IVIG）Gammaplex 5%和Gammaplex 10%在33名成人和15名原发性免疫缺陷病（PID）儿童中的安全性、耐受性和药代动力学。
符合条件的成人接受5次Gammaplex 5%输注，随后接受5次Gammaplex 10%输注，或反之，按21天或28天给药方案分层。儿科受试者仅接受5次Gammaplex 10%输注。
基于浓度-时间曲线下面积（AUC）值的Gammaplex 10%/Gammaplex 5%比值，达到了主要目标，即证明在28天给药间隔时Gammaplex 10%和Gammaplex 5%的生物等效性。在整个研究过程中，总免疫球蛋白G谷浓度得到良好维持，总值一般≥600mg/dL（研究纳入的最低水平）。在本研究使用的给药方案和输注速率下，接受Gammaplex 10%和5%治疗的成人和儿科PID受试者的安全性和耐受性相当且可接受。
在本项首次对PID受试者中5%IVIG和10%IVIG产品进行直接比较的研究中，药代动力学分析证明了在28天给药间隔时Gammaplex 10%和Gammaplex 5%的生物等效性。Gammaplex 10%制剂在儿科和成人PID受试者中安全且耐受性良好。基于这项PID受试者桥接研究的结果，预计Gammaplex 10%具有与已获许可的Gammaplex 5%相似的治疗效果——Gammaplex 5%已在PID和特发性血小板减少性紫癜患者中证明了疗效和耐受性。
