Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study

J Clin Immunol. 2021 Feb;41(2):458-469. doi: 10.1007/s10875-020-00912-5. Epub 2021 Jan 6.

Abstract

Purpose: To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (> 25 mL and > 25 mL/h per injection site) in patients with primary immunodeficiency.

Methods: The Hizentra® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25-50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25-100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated.

Results: Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study.

Conclusion: Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times.

Trial registration: NCT03033745 ; registered January 27, 2017.

Keywords: IgPro20; Primary immunodeficiency (PID); high infusion flow rate; high infusion volume; pump-assisted infusion; subcutaneous Ig (SCIG).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / immunology
  • Immunoglobulins, Intravenous / adverse effects
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / therapy*
  • Infusion Pumps / adverse effects
  • Infusions, Subcutaneous / adverse effects
  • Male
  • Middle Aged
  • Primary Immunodeficiency Diseases / immunology*
  • Primary Immunodeficiency Diseases / therapy*
  • Young Adult

Substances

  • Hizentra
  • Immunoglobulin G
  • Immunoglobulins, Intravenous

Associated data

  • ClinicalTrials.gov/NCT03033745