Multicenter Study

. 2022 Apr;42(3):500-511.

doi: 10.1007/s10875-021-01181-6. Epub 2022 Jan 1.

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

Manuel Santamaria¹, Olaf Neth², Jo A Douglass^{3

4}, Gergely Krivan⁵, Robin Kobbe⁶, Ewa Bernatowska⁷, Sofia Grigoriadou⁸, Claire Bethune⁹, Anita Chandra¹⁰, Gerd Horneff^{11

12}, Michael Borte¹³, Anja Sonnenschein¹⁴, Pavlina Kralickova¹⁵, Silvia Sánchez Ramón¹⁶, Daman Langguth¹⁷, Luis Ignacio Gonzalez-Granado¹⁸, Laia Alsina^{19

20

21}, Montse Querolt²², Rhonda Griffin²³, Carrie Hames²³, Elsa Mondou²³, Jeffrey Price²³, Ana Sanz²², Jiang Lin²³

Affiliations

¹ Unidad de Inmunologia Clinica, Hospital Universitario Reina Sofía, Facultad de Medicina, Universidad de Cordoba, Cordoba, Spain.
² 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.
³ Department of Immunology and Allergy, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁴ Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
⁵ Department for Paediatric Haematology and Hemopoietic Stem Cell Transplantation, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
⁶ First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.
⁸ Department of Immunology, The Royal London Hospital, Barts Health NHS Trust, London, UK.
⁹ Peninsula Immunology and Allergy Service, University Hospitals Plymouth, Plymouth, UK.
¹⁰ Department of Medicine, University of Cambridge, Cambridge, UK.
¹¹ Asklepios Kinderklinik Sankt Augustin, Sankt Augustin, Germany.
¹² University Hospital of Cologne, Cologne, Germany.
¹³ Klinikum St Georg GmbH, Klinik für Kinder- und Jugendmedizin, Leipzig, Germany.
¹⁴ Department of Pediatric Immunology and Rheumatology, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁵ Department of Allergology and Clinical Immunology, Faculty of Medicine, Charles University and University Hospital in Hradec Kralove, Hradec Kralove, Czechia.
¹⁶ Servicio de Inmunología, Hospital Clínico San Carlos, Madrid, Spain.
¹⁷ Immunology Department, Sullivan Nicolaides Pathology, Brisbane, Australia.
¹⁸ 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.
¹⁹ Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²⁰ Institut de Recerca Sant Joan de Déu, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²¹ Universitat de Barcelona, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²² Grifols Bioscience Research Group, Sant Cugat del Vallès, Barcelona, Spain.
²³ Grifols Bioscience Research Group, Research Triangle Park, NC, USA.

PMID: 34973143
PMCID: PMC9016006
DOI: 10.1007/s10875-021-01181-6

Multicenter Study

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

Manuel Santamaria et al. J Clin Immunol. 2022 Apr.

. 2022 Apr;42(3):500-511.

doi: 10.1007/s10875-021-01181-6. Epub 2022 Jan 1.

Authors

Affiliations

¹ Unidad de Inmunologia Clinica, Hospital Universitario Reina Sofía, Facultad de Medicina, Universidad de Cordoba, Cordoba, Spain.
² 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.
³ Department of Immunology and Allergy, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁴ Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
⁵ Department for Paediatric Haematology and Hemopoietic Stem Cell Transplantation, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
⁶ First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.
⁸ Department of Immunology, The Royal London Hospital, Barts Health NHS Trust, London, UK.
⁹ Peninsula Immunology and Allergy Service, University Hospitals Plymouth, Plymouth, UK.
¹⁰ Department of Medicine, University of Cambridge, Cambridge, UK.
¹¹ Asklepios Kinderklinik Sankt Augustin, Sankt Augustin, Germany.
¹² University Hospital of Cologne, Cologne, Germany.
¹³ Klinikum St Georg GmbH, Klinik für Kinder- und Jugendmedizin, Leipzig, Germany.
¹⁴ Department of Pediatric Immunology and Rheumatology, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁵ Department of Allergology and Clinical Immunology, Faculty of Medicine, Charles University and University Hospital in Hradec Kralove, Hradec Kralove, Czechia.
¹⁶ Servicio de Inmunología, Hospital Clínico San Carlos, Madrid, Spain.
¹⁷ Immunology Department, Sullivan Nicolaides Pathology, Brisbane, Australia.
¹⁸ 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.
¹⁹ Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²⁰ Institut de Recerca Sant Joan de Déu, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²¹ Universitat de Barcelona, Barcelona, Spain. lalsina@sjdhospitalbarcelona.org.
²² Grifols Bioscience Research Group, Sant Cugat del Vallès, Barcelona, Spain.
²³ Grifols Bioscience Research Group, Research Triangle Park, NC, USA.

PMID: 34973143
PMCID: PMC9016006
DOI: 10.1007/s10875-021-01181-6

Erratum in

Correction to: 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.
Santamaria M, Neth O, Douglass JA, Krivan G, Kobbe R, Bernatowska E, Grigoriadou S, Bethune C, Chandra A, Horneff G, Borte M, Sonnenschein A, Kralickova P, Ramón SS, Langguth DD, Gonzalez-Granado LI, Alsina L, Querolt M, Griffin R, Hames C, Mondou E, Price J, Sanz A, Lin J. Santamaria M, et al. J Clin Immunol. 2022 Apr;42(3):512-513. doi: 10.1007/s10875-022-01219-3. J Clin Immunol. 2022. PMID: 35174440 Free PMC article. No abstract available.

Abstract

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.

Keywords: 20% immunoglobulin; GTI1503; Primary immunodeficiency; immunoglobulin replacement therapy; subcutaneous.

PubMed Disclaimer

Conflict of interest statement

MQ, RG, CH, EM, JP, AS, and JL are employed by Grifols Bioscience Research Group, maker of IGSC 20%. All other authors declare no competing interests.

Figures

**Fig. 1**
Subject Disposition^a. ^aOne subject who was screened and entered into the previous regimen phase was withdrawn at sponsor’s request prior to receiving any amount of IGSC 20% due to reported serious adverse events (non-productive cough with accompanying cyanosis, hypoxemia, interstitial pneumonitis) ^bRefers to the first 13 weeks of treatment ^cRefers to the next 39 weeks of treatment

See this image and copyright information in PMC

References

1. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991;325(2):110–117. doi: 10.1056/nejm199107113250207. - DOI - PubMed
1. Sacher RA. Intravenous immunoglobulin consensus statement. J Allergy Clin Immunol. 2001;108(4 Suppl):S139–S146. doi: 10.1067/mai.2001.118640. - DOI - PubMed
1. Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs. 2007;21(2):105–116. doi: 10.2165/00063030-200721020-00005. - DOI - PubMed
1. Helbert M, Farragher A. Subcutaneous immunoglobulin for patients with antibody deficiency. Br J Hosp Med (Lond). 2007;68(4):206–10. doi: 10.12968/hmed.2007.68.4.206. - DOI - PubMed
1. Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26(3):265–273. doi: 10.1007/s10875-006-9021-7. - DOI - PubMed

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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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources

Research Materials

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