Efficacy and safety of Gammaplex® 5% in children and adolescents with primary immunodeficiency diseases

Abstract

SummaryThis open-label multi-centre study evaluated Gammaplex V R 5%, a human intravenous immunoglobulin (IVIG) 5% liquid, in 25 children and adolescent patients (aged 3-16 years) with primary immunodeficiency diseases (PIDs). Subjects received Gammaplex 5% (at doses of 300-800 mg/kg/infusion) for 12 months, with a 3-month follow-up. The primary efficacy end-point was the incidence of serious acute bacterial infections (SABIs) during the 12-month treatment period. Secondary objectives assessed safety and tolerability. Nineteen males and six females were treated using the same infusion schedule as their prior IVIG treatment (14 and 11 subjects on 21-and 28-day dosing schedules, respectively). Two SABIs of pneumonia were reported, resulting in an annual SABI event rate of 0Á09 [upper one-sided 99% confidence interval (CI) 5 0Á36]. Twenty-one subjects (84%) experienced ! 1 infection during the study, with a median infective episode per subject/year of 3Á08 (range 5 0-10Á4). Sixteen subjects (64%) missed ! 1 day of nursery or school because of infection or other illness. All trough immunoglobulin G levels exceeded 7Á00 g/l after 15 weeks (mean 5 9Á69 g/l; range 5 7Á04-15Á35 g/l). Product-related adverse events occurred in 14 subjects (56%); none were serious. Of 368 total infusions, 97 (26%) were associated temporally with an adverse event ( 72 h after infusion), regardless of causality. Laboratory test results and adverse-reaction data showed no evidence of product-related haemolysis or thromboembolic events. These data demonstrate that Gammaplex 5% is effective in preventing SABIs and well tolerated in children and adolescents with PID.

Incidence and risk factors for intravenous immunoglobulin‐related hemolysis: A systematic review of clinical trial and real‐world populations

“…In studies that reported IVIG dose and product, the majority of hemolytic events occur with IVIG products produced by ethanol‐OA fractionation given at a high dose (≥2 g/kg), with incidence rates of 0.7%–21.1% observed 18,24 . Only a few hemolytic events have been reported when products produced by Cohn fractionation, ethanol‐PEG, and ethanol‐OA plus IAC were given 22,27 . This suggests an association between an increased risk of hemolysis with increased amounts of isoagglutinins administered to the patient.…”

“…The estimated incidence of hemolysis ranged from 0% to 21% in clinical trials (Table 1). 23,24,27,28 Two studies reported the blood group details of the whole study population and blood group details of patients with hemolysis. 24,26 A higher proportion of hemolysis cases were experienced in patients with blood group A or AB than in blood groups B or O.…”

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex® 10% Versus Gammaplex® 5% in Subjects with Primary Immunodeficiency

“…The Gammaplex 10% formulation was also safe and well tolerated in pediatric subjects with PID. Based on the bioequivalence and PK analysis from this bridging study in PID subjects, Gammaplex 10% can be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated tolerability and efficacy in adult and pediatric patients with PID and ITP [ 11 – 13 ].…”

“…Previous studies of Gammaplex 5% demonstrated efficacy in preventing serious acute bacterial infections (SABIs) and demonstrated tolerability both in patients with PID [11, 12] and those with ITP [13]. Like Gammaplex 5% (Gammaplex [5%] 5 g in 100 mL), Gammaplex 10% (Gammaplex [10%] 10 g in 100 mL) is a ready-prepared solution for IV administration containing the active ingredient human normal IgG.…”

“…Gammaplex ® 5% is a highly purified human IgG liquid product intended for intravenous (IV) administration (Bio Products Laboratory Ltd., Elstree, UK) and approved for use in the USA and the UK for PID and immune thrombocytopenic purpura (ITP) [ 9 , 10 ]; Gammaplex 5% is also licensed in Brazil, Brunei, Israel, Lebanon, and Malta. Previous studies of Gammaplex 5% demonstrated efficacy in preventing serious acute bacterial infections (SABIs) and demonstrated tolerability both in patients with PID [ 11 , 12 ] and those with ITP [ 13 ]. Like Gammaplex 5% (Gammaplex [5%] 5 g in 100 mL), Gammaplex 10% (Gammaplex [10%] 10 g in 100 mL) is a ready-prepared solution for IV administration containing the active ingredient human normal IgG.…”