Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX®-C) in Pediatric Patients with Primary Immunodeficiency Disease.

Abstract

PURPOSE:

This phase 4, multicenter, open-labeled, single-sequence, crossover study in pediatric patients (ages 2 to 16) with primary immunodeficiency disease (PID) evaluated the pharmacokinetics, safety, and tolerability for subcutaneously (SC) administered 10 % caprylate/chromatography purified human immune globulin injection (IGIV-C, GAMUNEX®) compared with intravenously (IV) administered IGIV-C.

METHODS:

This study included a screening phase, run-in phase (where required), IV treatment phase, SC treatment phase, and end of study/early termination visit. Eligible patients receiving a stable dose of IGIV-C entered into the IV phase to receive two IV infusions of IGIV-C (200-600 mg/kg per infusion) every 3-4 weeks. The weekly SC dose of IGIV-C was calculated using a conversion factor of 1.37 times the prior IV dose.

RESULTS:

Twelve subjects between the ages of 2 and 16 years participated in the clinical study with the median age being 11 years old. The adjusted weekly mean AUC0-τ,IV was 216,873.7 h*mg/dL for the IV phase versus a mean AUC0-τ,SC of 230,830.0 h*mg/dL for the SC phase. The mean (range) C trough was 997.2 (784-1320) mg/dL in the IV phase and 1325.0 (1077-1690) mg/dL in the SC phase. During the SC phase, 100.0 % of the patients (n = 11) experienced treatment-emergent adverse events (TEAEs) that were local infusion reactions and 9 patients (81.8 %) had TEAEs that were non-infusion site reactions. The majority of TEAEs were mild or moderate in severity.

CONCLUSION:

In pediatric patients with PID, SC-administered IGIV-C provides comparable overall serum exposure to total IgG to that produced by IV-administered IGIV-C. We have concluded that weekly SC administration of 10 % IGIV-C based on a dose conversion factor of 1.37 is safe and well-tolerated in pediatric patients with PID.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT01465958. https://clinicaltrials.gov/ct2/show/NCT01465958?term=NCT01465958.&rank=1.

• Authors: Jennifer Heimall, Junliang Chen, Joseph A Church, Rhonda Griffin, Isaac Melamed, Gary I Kleiner
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 36 Issue 6 Pg. 600-9 (08 2016) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 27342758 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Immunoglobulins, Intravenous

Topics

• Adolescent
• Antibodies, Neutralizing (blood)
• Area Under Curve
• Bacterial Infections (etiology)
• Child
• Child, Preschool
• Drug Monitoring
• Female
• Humans
• Immunoglobulins, Intravenous (pharmacology, therapeutic use)
• Immunologic Deficiency Syndromes (blood, diagnosis, drug therapy)
• Injection Site Reaction (etiology)
• Male
• Treatment Outcome