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

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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

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Acknowledgments

Grifols, Bioscience Industrial Group, would like to acknowledge the investigators, the site personnel, and the patients who participated in this study. Also, Cristina Cruz (Grifols, Bioscience Industrial Group), who provided oversight for the in-house measles antibody testing; Susan Sorrells and Kim Hanna (Grifols, Bioscience Industrial Group) for their critical review of the manuscript; and Toya Lennon (Grifols, Bioscience Industrial Group) who provided study conduct oversight and review of the manuscript. This study was sponsored by Grifols Therapeutics Inc. Grifols manufactures GAMUNEX®-C. Medical writing assistance was provided under the direction of the authors by Latoya M. Mitchell, PhD, CMPP, of Grifols.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Clinical Immunology and Allergy, Children’s Hospital Los Angeles, Los Angeles, CA, 90027, USA

    Joseph A. Church

  2. Grifols, Bioscience Industrial Group, Research Triangle Park, NC, 27709, USA

    Junliang Chen & Rhonda Griffin

  3. IMMUNOe Research Centers, Centennial, CO, 80112, USA

    Isaac Melamed

  4. Pediatric Allergy and Immunology, Joe DiMaggio Children’s Hospital, Hollywood, FL, 33021, USA

    Gary I. Kleiner

  5. Division of Allergy and Immunology, Department of Pediatrics, The Children’s Hospital of Philadelphia, 3550 Market Street, Philadelphia, PA, 19104, USA

    Jennifer Heimall

Authors
  1. Jennifer Heimall
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  2. Junliang Chen
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  3. Joseph A. Church
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  4. Rhonda Griffin
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  5. Isaac Melamed
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  6. Gary I. Kleiner
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Corresponding author

Correspondence to Jennifer Heimall.

Ethics declarations

The study was approved by all participating centers’ institutional review boards, and the investigators ensured that the study was conducted in full conformance with appropriate laws, regulations, and the 1964 Declaration of Helsinki. Written informed consent was obtained from each patient and/or legal guardian, and all patients provided assent.

Conflict of Interest

Junliang Chen and Rhonda Griffin are employees of Grifols, Bioscience Industrial Group. Drs. Heimall, Church, Melamed, and Kleiner served as primary investigators for this study. Dr. Church has received funding from BioProducts Laboratory, LTD; BD Biosciences, Inc; and Prometic Biotherapeutics. No other potential conflicts of interest were reported.

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Heimall, J., Chen, J., Church, J.A. et al. 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 36, 600–609 (2016). https://doi.org/10.1007/s10875-016-0311-4

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  • DOI: https://doi.org/10.1007/s10875-016-0311-4

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