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A Multi-Center, Open-Label, Single-Arm Trial to Evaluate the Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency

M. Santamaria, O. Neth, JA. Douglass, G. Krivan, R. Kobbe, E. Bernatowska, S. Grigoriadou, C. Bethune, A. Chandra, G. Horneff, M. Borte, A. Sonnenschein, P. Kralickova, SS. Ramón, D. Langguth, LI. Gonzalez-Granado, L. Alsina, M. Querolt, R....

. 2022 ; 42 (3) : 500-511. [pub] 20220101

Language English Country Netherlands

Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22018992

PURPOSE: The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). METHODS: Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject's previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. RESULTS: Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12-16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008-0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83-1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. CONCLUSIONS: IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.

1st Department of Medicine Division of Infectious Diseases University Medical Center Hamburg Eppendorf Hamburg Germany

Asklepios Kinderklinik Sankt Augustin Sankt Augustin Germany

Clinical Immunology and Primary Immunodeficiencies Unit Pediatric Allergy and Clinical Immunology Department Hospital Sant Joan de Déu Barcelona Spain

Department for Paediatric Haematology and Hemopoietic Stem Cell Transplantation Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases Budapest Hungary

Department of Allergology and Clinical Immunology Faculty of Medicine Charles University and University Hospital in Hradec Kralove Hradec Kralove Czechia

Department of Immunology and Allergy The Royal Melbourne Hospital Melbourne VIC Australia

Department of Immunology Children's Memorial Health Institute Warsaw Poland

Department of Immunology The Royal London Hospital Barts Health NHS Trust London UK

Department of Medicine The University of Melbourne Melbourne VIC Australia

Department of Medicine University of Cambridge Cambridge UK

Department of Pediatric Immunology and Rheumatology University Medical Center of Johannes Gutenberg University Mainz Mainz Germany

Grifols Bioscience Research Group Research Triangle Park NC USA

Grifols Bioscience Research Group Sant Cugat del Vallès Barcelona Spain

Immunology Department Sullivan Nicolaides Pathology Brisbane Australia

Institut de Recerca Sant Joan de Déu Barcelona Spain

Klinikum St Georg GmbH Klinik für Kinder und Jugendmedizin Leipzig Germany

Pediatric Infectious Diseases Rheumatology and Immunology Unit Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla Universidad de Sevilla CSIC Red de Investigación Traslacional en Infectología Pediátrica RITIP IBiSSeville Spain

Peninsula Immunology and Allergy Service University Hospitals Plymouth Plymouth UK

Primary Immunodeficiencies Unit Hospital Universitario 12 de Octubre and Department of Public and Maternal Child Health Faculty of Medicine Complutense University of Madrid Madrid Spain

Servicio de Inmunología Hospital Clínico San Carlos Madrid Spain

Unidad de Inmunologia Clinica Hospital Universitario Reina Sofía Facultad de Medicina Universidad de Cordoba Cordoba Spain

Universitat de Barcelona Barcelona Spain

University Hospital of Cologne Cologne Germany

References provided by Crossref.org

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