Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies.
A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient-year, P < 0·0001); the rate of all infections was 4·38/patient-year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3-4·1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.
Klinikum St Georg GmbH, Klinik für Kinder- und Jugendmedizin, Leipzig, Germany.
M
M
Borte
United St Istvan and St Laszlo Hospital, Budapest, Hungary.
G
G
Kriván
2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.|Dalhousie University, IWK Health Centre, Halifax, Canada.
B
B
Derfalvi
Department of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, Hungary.
L
L
Maródi
Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen-Nürnberg, Germany.
T
T
Harrer
Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK.
S
S
Jolles
Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
C
C
Bourgeois
Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
W
W
Engl
Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
H
H
Leibl
Baxalta US Inc., now part of Shire, Cambridge, MA, USA.
B
B
McCoy
Baxalta US Inc., now part of Shire, Westlake Village, CA, USA.
D
D
Gelmont
Baxalta US Inc., now part of Shire, Cambridge, MA, USA.|University of California Irvine, Irvine, CA, USA.
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L
Yel
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
D016756:Immunoglobulins, Intravenous
20% immunoglobulin; immunoglobulin replacement therapy; pharmacokinetics; primary immunodeficiency diseases; subcutaneous administration