title: Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX®-C) in Pediatric Patients with Primary Immunodeficiency Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov identifier: NCT01465958. https://clinicaltrials.gov/ct2/show/NCT01465958?term=NCT01465958.&rank=1.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3550 Market Street, Philadelphia, PA, 19104, USA. heimallj@email.chop.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heimall
authors.affiliation: Grifols, Bioscience Industrial Group, Research Triangle Park, NC, 27709, USA.
authors.forename: Junliang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Church
authors.affiliation: Grifols, Bioscience Industrial Group, Research Triangle Park, NC, 27709, USA.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Griffin
authors.affiliation: IMMUNOe Research Centers, Centennial, CO, 80112, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Melamed
authors.affiliation: Pediatric Allergy and Immunology, Joe DiMaggio Children's Hospital, Hollywood, FL, 33021, USA.
authors.forename: Gary I
authors.initials: GI
authors.lastname: Kleiner
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood; D019540:Area Under Curve; D001424:Bacterial Infections / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use*; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000075662:Injection Site Reaction / Q000209:etiology; D008297:Male; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D016756:Immunoglobulins, Intravenous
keywords: GAMUNEX®-C; IGIV-C; Primary immunodeficiency; intravenous immune globulin; pharmacokinetics; subcutaneous immune globulin