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

J Clin Immunol. 2016 Aug;36(6):600-9. doi: 10.1007/s10875-016-0311-4. Epub 2016 Jun 25.

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.

Keywords: GAMUNEX®-C; IGIV-C; Primary immunodeficiency; intravenous immune globulin; pharmacokinetics; subcutaneous immune globulin.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Neutralizing
  • Immunoglobulins, Intravenous

Associated data

  • ClinicalTrials.gov/NCT01465958