Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study

Juthaporn Cowan, Vincent R Bonagura, Patricia L Lugar, Paul J Maglione, Niraj C Patel, Donald C Vinh, Jutta H Hofmann, Michaela Praus, Mikhail A Rojavin, Juthaporn Cowan, Vincent R Bonagura, Patricia L Lugar, Paul J Maglione, Niraj C Patel, Donald C Vinh, Jutta H Hofmann, Michaela Praus, Mikhail A Rojavin

Abstract

Purpose: To evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5-2.0 mL/min.

Methods: Patients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra® Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated.

Results: Sixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103-108 to 23-28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L).

Conclusions: Subcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID.

Trial registration: NCT03033745.

Keywords: IgG; Primary immunodeficiency (PID); high infusion rate; manual push; subcutaneous Ig (SCIG).

Conflict of interest statement

JC has received research funding from CSL Behring and Octapharma and is a clinical trial site investigator for Takeda. VRB has served as a speaker for CSL Behring and Takeda. PLL is a clinical trial site investigator for CSL Behring and Takeda. PJM has received research funding from the National Institutes of Health, the AAAAI Foundation, Boston University, Takeda, and Horizon Pharma. NCP has served as a speaker for CSL Behring and Takeda; has received research funding from CSL Behring and Takeda; and has served as an advisory board member for Horizon Therapeutics. DCV has received research funding from the Fonds de la recherche en santé du Quebec, Canadian Institutes of Health Research, the U.S. Department of Defense, the Jeffrey Modell Foundation, La Fondation du Grand Défi Pierre Lavoie, and CSL Behring; has served as a speaker for CSL Behring and Avir Pharma; and has received clinical trial funding from CSL Behring and Cidara Therapeutics. MAR, MP, and JHH are employees of CSL Behring and own CSL Behring shares.

Figures

Fig. 1
Fig. 1
Patient disposition. Disposition of patients in the HILO study with a focus on the Manual Push Flow Rate Cohort
Fig. 2
Fig. 2
Responder analysis of increasing manual push flow rates (safety analysis set). Responders were patients who achieved the prespecified minimum of valid infusions at a certain level. The percentage of responders at each flow rate is based on all patients in the Manual Push Flow Rate Cohort (n = 16). The prespecified success criterion was a responder rate of ≥ 33% for each flow rate (dashed line). Non-responders were patients who did not meet the minimum number of valid infusions at a given flow rate during the 4 weeks planned for that flow rate. The number of responders for each flow rate is shown at the bottom of each bar (underlined). aBefore the start date of non-response
Fig. 3
Fig. 3
Mean weekly infusion duration with increasing flow rates (safety analysis set). The mean weekly infusion time for the Manual Push Flow Rate Cohort at the indicated flow rates. The number of patients with infusion duration data for each week (n) is shown below each bar. Error bars indicate SD. SD, standard deviation
Fig. 4
Fig. 4
Median cumulative weekly IgPro20 volume and dose administered per patient (safety analysis set). The cumulative median weekly volume (mL) and dose (mg/kg) of IgPro20 administered per patient during the study; each dot represents an individual patient. Owing to differences in patient body weight, individual volumes administered vary even if the dose is the same, as volume depends on body weight

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