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

ABSTRACT: 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.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.Eighty-three subjects (24?

SUBMITTER: Wasserman RL

PROVIDER: S-EPMC4940441 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Wasserman Richard L RL Melamed Isaac I Stein Mark R MR Engl Werner W Sharkhawy Marlies M Leibl Heinz H Puck Jennifer J Rubinstein Arye A Kobrynski Lisa L Gupta Sudhir S Grant Andrew J AJ Ratnayake Anoshie A Richmond Wendell G WG Church Joseph J Yel Leman L Gelmont David D

Journal of clinical immunology 20160525 6

<h4>Purpose</h4>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.<h4>Methods</h4>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 rH ...[more]

PMID: 27220317

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A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)

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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.

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Project description:PurposeTo 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.MethodsPatients 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.ResultsSixteen 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).ConclusionsSubcutaneous 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 registrationNCT03033745.

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Safety, tolerability and pharmacokinetics of subcutaneous and intravenous anifrolumab in healthy volunteers.

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