Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency

• Type of Material: Article
• Authors: Richard L. Wasserman, Allergy Partners of North Texas Research; Isaac Melamed, IMMUNOe Clinical Research Center; Mark R. Stein, Allergy Associates of the Palm Beaches; Werner Engl, Baxalta Innovations GmbH; Marlies Sharkhawy, Baxalta Innovations GmbH; Heinz Leibl, Baxalta Innovations GmbH; Jennifer Puck, University of California San Francisco; Arye Rubinstein, Montefiore Medical Center; Lisa Kobrynski, Emory University; Sudhir Gupta, University of California Irvine; Andrew J. Grant, University of Texas; Anoshie Ratnayake, West Coast Clinical Trials; Wendell G. Richmond, Allergy and Asthma Physicians; Joseph Church, Children’s Hospital Los Angeles; Leman Yel, Baxalta US Inc.; David Gelmont, Baxalta US Inc.
• Language: English
• Date: 2016-08-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Final Published Version
• Copyright Statement: © 2016, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10875-016-0298-x
• Title of Journal or Parent Work: Journal of Clinical Immunology
• ISSN: 0271-9142
• Volume: 36
• Issue: 6
• Start Page: 571
• End Page: 582
• Grant/Funding Information: This clinical investigation was sponsored by Baxalta US Inc., Westlake Village, CA.
• Keywords: Life Sciences & Biomedicine; Immunology; efficacy; Subcutaneous IgG replacement; GAMMA-GLOBULIN; HOME TREATMENT; primary immunodeficiency; ANTIBODY DEFICIENCIES; recombinant human hyaluronidase; tolerability; LIQUID; CHILDREN; IGG SELF-INFUSIONS; Science & Technology; REPLACEMENT THERAPY; QUALITY-OF-LIFE; DISEASES
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

Purpose: Treatment of primary immunodeficiency diseases (PIDD) with subcutaneous (SC) infusions of IgG preceded by injection of recombinant human hyaluronidase (rHuPH20) (IGHy) to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies. Methods: Subjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous (IV) dose, facilitated by prior injection of 75 U/g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased (ramped-up) to a 3- or 4-week schedule. Results: Eighty-three subjects (24 < 18 years; 59 ≥ 18 years) received 2729 infusions (excluding ramp-up) at a mean dose of 0.155 g/kg/week in the pivotal and 0.156 g/kg/week in the extension study. IGHy exposure exceeded 30 months in 48 subjects. During 187.7 subject-years of IGHy exposure, 2005 adverse events (AEs) (10.68 per subject-year) occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1–12 to approximately 1.50/subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160. The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years. Conclusions: Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.