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


METHODS
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.


RESULTS
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 (AUC0-28) 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%.


CONCLUSIONS
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.
Allergy Partners of North Texas Research, Dallas, TX, USA.
Richard L
RL
Wasserman
IMMUNOe International Research Centers, Centennial, CO, USA.
Isaac R
IR
Melamed
Allergy Associates of the Palm Beaches, North Palm Beach, FL, USA.
Mark R
MR
Stein
Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK.
Stephen
S
Jolles
Bio Products Laboratory Ltd., Dagger Lane, Elstree, Hertfordshire, UK. miranda.norton@bpl.co.uk.
Miranda
M
Norton
Section of Allergy and Immunology, Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, USA.
James N
JN
Moy
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous
Gammaplex® 10%; Gammaplex® 5%; Primary immunodeficiency disease (PID); intravenous immunoglobulin (IVIG)