Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency

John B Hagan, Mary B Fasano, Sheldon Spector, Richard L Wasserman, Isaac Melamed, Mikhail A Rojavin, Othmar Zenker, Jordan S Orange, John B Hagan, Mary B Fasano, Sheldon Spector, Richard L Wasserman, Isaac Melamed, Mikhail A Rojavin, Othmar Zenker, Jordan S Orange

Abstract

Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5-72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs.

Figures

Fig. 1
Fig. 1
Serum IgG trough levels (patients with PID). Blood samples were taken before infusion start at screening (S); at weeks 1, 2, 3, 4, 8, and 12; every 4 weeks thereafter; and at the completion visit (CV). For most infusions and for the completion visit, data from at least 29 patients were available; for the following infusions, the number of patients with available data was lower: infusion 60, n = 28; infusion 64, n = 27. Note that the patient’s regular IVIG infusion was given just after screening, and SCIG administration was begun 1 week later
Fig. 2
Fig. 2
Rate of injection site reactions over time (patients with PID). Investigator assessments were performed at 15 to 45 minutes after infusion at study visits (every 4 weeks). Patient assessments were made 24 ± 3 hours after every infusion until the completion visit (week 66). For both assessments, the number of infusions with available data decreased from 49 at week 1 to 28 at week 64

References

    1. Primary immunodeficiency diseases: report of an IUIS Scientific Committee. Clin Exp Immunol. 1999;118:1–28.
    1. Buckley RH. Primary immunodeficiency diseases due to defects in lymphocytes. N Engl J Med. 2000;343:1313–1324. doi: 10.1056/NEJM200011023431806.
    1. Chapel H, Geha R, Rosen F. Primary immunodeficiency diseases: an update. Clin Exp Immunol. 2003;132:9–15. doi: 10.1046/j.1365-2249.2003.02110.x.
    1. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. doi: 10.1006/clim.1999.4725.
    1. Ochs HD, Smith CIE, Puck JM. Primary immunodeficiency diseases: a molecular and genetic approach. Second. New York: Oxford University Press Inc, USA; 2007.
    1. Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease. Lancet. 2008;372:489–502. doi: 10.1016/S0140-6736(08)61199-X.
    1. Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am. 2008;28:413–437. doi: 10.1016/j.iac.2008.01.008.
    1. Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109:1001–1004. doi: 10.1067/mai.2002.124999.
    1. Bussel JB, Eldor A, Kelton JG, Varon D, Brenner B, Gillis S, et al. IGIV-C, a novel intravenous immunoglobulin: evaluation of safety, efficacy, mechanisms of action, and impact on quality of life. Thromb Haemost. 2004;91:771–778.
    1. Church JA, Borte M, Taki H, Nelson RP, Sleasman JW, Knutsen AP, et al. Efficacy and safety of Privigen in children and adolescents with primary immunodeficiency. Pediatr Asthma Allergy Immunol. 2009;22:53–62. doi: 10.1089/pai.2009.0005.
    1. de Gracia J. Vendrell M, Alvarez A, Pallisa E, Rodrigo MJ, de la RD, et al. Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency. Int Immunopharmacol. 2004;4:745–753.
    1. Eijikhout HW, van der Meer JW, Kallenberg CG, Weening RS, van Dissel JT, Sanders LA, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001;135:165–174.
    1. Gardulf A, Hammarstrom L, Smith CI. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet. 1991;338:162–166. doi: 10.1016/0140-6736(91)90147-H.
    1. Stein MR, Nelson RP, Church JA, Wasserman RL, Borte M, Vermylen C, et al. Safety and efficacy of Privigen®, a novel 10% liquid immunoglobulin preparation for intravenous use, in patients with primary immunodeficiencies. J Clin Immunol. 2009;29:137–144. doi: 10.1007/s10875-008-9231-2.
    1. Abrahamsen TG, Sandersen H, Bustnes A. Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics. 1996;98:1127–1131.
    1. Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. 2008;28:779–802. doi: 10.1016/j.iac.2008.07.002.
    1. Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20:94–100. doi: 10.1023/A:1006678312925.
    1. Gardulf A, Andersen V, Bjorkander J, Ericson D, Froland SS, Gustafson R, et al. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet. 1995;345:365–369. doi: 10.1016/S0140-6736(95)90346-1.
    1. Gardulf A, Nicolay U, Asensio O, Bernatowska E, Bock A, Carvalho BC, et al. Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies—a prospective, multi-national study. J Clin Immunol. 2006;26:177–185. doi: 10.1007/s10875-006-9002-x.
    1. Gardulf A, Nicolay U. Replacement IgG therapy and self-therapy at home improve the health-related quality of life in patients with primary antibody deficiencies. Curr Opin Allergy Clin Immunol. 2006;6:434–442. doi: 10.1097/01.all.0000246619.49494.41.
    1. Hansen S, Gustafson R, Smith CI, Gardulf A. Express subcutaneous IgG infusions: decreased time of delivery with maintained safety. Clin Immunol. 2002;104:237–241. doi: 10.1006/clim.2002.5215.
    1. Stiehm ER, Casillas AM, Finkelstein JZ, Gallagher KT, Groncy PM, Kobayashi RH, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product. J Allergy Clin Immunol. 1998;101:848–849. doi: 10.1016/S0091-6749(98)70314-8.
    1. Welch MJ, Stiehm ER. Slow subcutaneous immunoglobulin therapy in a patient with reactions to intramuscular immunoglobulin. J Clin Immunol. 1983;3:285–286. doi: 10.1007/BF00915353.
    1. Stucki M, Boschetti N, Schaefer W, Hostettler T, Kaesermann F, Nowak T, et al. Investigations of prion and virus safety of a new liquid IVIG product. Biologicals. 2008;36:239–247. doi: 10.1016/j.biologicals.2008.01.004.
    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;26:265–273. doi: 10.1007/s10875-006-9021-7.
    1. FDA. Safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. Guidance for industry; 2008.
    1. Quartier P, Debre M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999;134:589–596. doi: 10.1016/S0022-3476(99)70246-5.
    1. Church JA, Leibl H, Stein MR, Melamed IR, Rubinstein A, Schneider LC, et al. Efficacy, safety and tolerability of a new 10% liquid intravenous immune globulin [IGIV 10%] in patients with primary immunodeficiency. J Clin Immunol. 2006;26:388–395. doi: 10.1007/s10875-006-9025-3.
    1. Roifman CM, Schroeder H, Berger M, Sorensen R, Ballow M, Buckley RH, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial. Int Immunopharmacol. 2003;3:1325–1333. doi: 10.1016/S1567-5769(03)00134-6.
    1. Dave S, Hagan J. Myocardial infarction during intravenous immunoglobulin infusion in a 65-year-old man with common variable immunodeficiency and subsequent successful repeated administration. Ann Allergy Asthma Immunol. 2007;99:567–570. doi: 10.1016/S1081-1206(10)60388-2.
    1. Caress JB, Hobson-Webb L, Passmore LV, Finkbiner AP, Cartwright MS. Case-control study of thromboembolic events associated with IV immunoglobulin. J Neurol. 2009;256:339–342. doi: 10.1007/s00415-009-0969-0.
    1. Brown HC, Ballas ZK. Acute thromboembolic events associated with intravenous immunoglobulin infusion in antibody-deficient patients. J Allergy Clin Immunol. 2003;112:797–799. doi: 10.1016/S0091-6749(03)01780-9.
    1. Stiehm ER. Human intravenous immunoglobulin in primary and secondary antibody deficiencies. Pediatr Infect Dis J. 1997;16:696–707. doi: 10.1097/00006454-199707000-00012.
    1. European Agency for the Evaluation of Medicinal Products (EMEA), Committee for Proprietary Medicinal Products (CPMP). Note for guidance on the clinical investigation of human normal immunoglobulin for subcutaneous and intramuscular use. EMEA/CPMP/BPWG/283/00; 2002
    1. Kittner JM, Grimbacher B, Wulff W, Jager B, Schmidt RE. Patients' attitude to subcutaneous immunoglobulin substitution as home therapy. J Clin Immunol. 2006;26:400–405. doi: 10.1007/s10875-006-9031-5.

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