Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies

Clin Exp Immunol. 2017 Jan;187(1):146-159. doi: 10.1111/cei.12866. Epub 2016 Oct 18.

Abstract

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient-year, P < 0·0001); the rate of all infections was 4·38/patient-year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3-4·1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.

Keywords: 20% immunoglobulin; immunoglobulin replacement therapy; pharmacokinetics; primary immunodeficiency diseases; subcutaneous administration.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Europe
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / pharmacokinetics
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Deficiency Syndromes / drug therapy*
  • Infusions, Subcutaneous
  • Male
  • Middle Aged
  • Prospective Studies
  • Young Adult

Substances

  • Immunoglobulins, Intravenous