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 (Jan, 10.1007/s10875-021-01181-6, 2022)

被引：0

作者：

Santamaria, Manuel ^{[1
]}

Neth, Olaf ^{[2
]}

Douglass, Jo A. ^{[3
,4
]}

Krivan, Gergely ^{[5
]}

Kobbe, Robin ^{[6
]}

Bernatowska, Ewa ^{[7
]}

Grigoriadou, Sofia ^{[8
]}

Bethune, Claire ^{[9
]}

Chandra, Anita ^{[10
]}

Horneff, Gerd ^{[11
,12
]}

Borte, Michael ^{[13
]}

Sonnenschein, Anja ^{[14
]}

Kralickova, Pavlina ^{[15
,16
]}

Ramon, Silvia Sanchez ^{[17
]}

Langguth, Daman D. ^{[18
]}

Gonzalez-Granado, Luis Ignacio ^{[19
,20
]}

Alsina, Laia ^{[21
,22
,23
]}

Querolt, Montse ^{[24
]}

Griffin, Rhonda ^{[25
]}

Hames, Carrie ^{[25
]}

Mondou, Elsa ^{[25
]}

Price, Jeffrey ^{[25
]}

Sanz, Ana ^{[24
]}

Lin, Jiang ^{[25
]}

机构：

[1] Univ Cordoba, Fac Med, Hosp Univ, Unidad Inmunol Clin, Cordoba, Spain

[2] Univ Seville, Hosp Univ Virgen del Rocio, Red Invest Traslac Infectol Pediat RITIP, Inst Biomed Sevilla,CSIC,IBiSSeville,Pediat Infec, Seville, Spain

[3] Royal Melbourne Hosp, Dept Immunol & Allergy, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Med, Melbourne, Vic, Australia

[5] Szent Laszlo Hosp, Paediat Haematol & Stem Cell Transplantat, Budapest, Hungary

[6] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Div Infect Dis, Hamburg, Germany

[7] Childrens Mem Hlth Inst, Dept Immunol, Warsaw, Poland

[8] Barts Hlth NHS Trust, Royal London Hosp, Dept Immunol, London, England

[9] Univ Hosp Plymouth, Peninsula Immunol & Allergy Serv, Plymouth, Devon, England

[10] Univ Cambridge, Dept Med, Cambridge, England

[11] Asklepios Kinderklin Sankt Augustin, St Augustin, Germany

[12] Univ Hosp Cologne, Cologne, Germany

[13] Klinikum St Georg GmbH, Klin Kinder & Jugendmed, Leipzig, Germany

[14] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pediat Immunol & Rheumatol, Mainz, Germany

[15] Charles Univ Prague, Fac Med, Dept Allergol & Clin Immunol, Hradec Kralove, Czech Republic

[16] Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic

[17] Hosp Clin San Carlos, Serv Inmunol, Madrid, Spain

[18] Sullivan Nicolaides Pathol, Dept Immunol, Brisbane, Qld, Australia

[19] Univ Complutense Madrid, Hosp Univ 12 Octubre, Primary Immunodeficiencies Unit, Madrid, Spain

[20] Univ Complutense Madrid, Fac Med, Dept Publ & Maternal Child Hlth, Madrid, Spain

[21] Hosp St Joan de Deu, Pediat Allergy & Clin Immunol Dept, Clin Immunol & Primary Immunodeficiencies Unit, Planta 3 Consultes Externes, Barcelona 08950, Spain

[22] Inst Recerca St Joan de Deu, Barcelona, Spain

[23] Univ Barcelona, Barcelona, Spain

[24] Grifols Biosci Ind Grp, Barcelona, Spain

[25] Grifols Biosci R&D, Res Triangle Pk, NC USA

来源：

JOURNAL OF CLINICAL IMMUNOLOGY | 2022年 / 42卷 / 03期

关键词：

20% immunoglobulin; GTI1503; immunoglobulin replacement therapy; Primary immunodeficiency; subcutaneous;

D O I：

10.1007/s10875-022-01219-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. © 2021, The Author(s).

引用

页码：512 / 513

页数：2