safety and pharmacokinetics of igsc 20% in subjects with primary immunodeficiency

Conditions: Primary Immunodeficiency

Summary: this study was designed to determine a dose of weekly subcutaneously administered immune globulin subcutaneous (human), 20% caprylate/chromatography purified (grifols) (igsc 20%) that produces steady-state auc of total igg that was non-inferior to that of the regularly administered intravenous dose of immune globulin injection (human), 10% caprylate/chromatography purified (grifols) (igiv-c 10%) in primary immunodeficiency subjects. this study was also designed to determine steady state trough total igg levels after igsc 20% infusion and after igiv-c 10% infusion for comparison and to assess the safety and tolerability of igsc 20%.

this was a prospective, multi-center, open-label, single-sequence, 6-month, pharmacokinetic, safety and tolerability study of igsc 20% in subjects with primary immunodeficiency. approximately 50 subjects were to be enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 2-16 years) completing treatment with subcutaneously administered igsc 20%. this study included 3 treatment phases: run-in phase, iv phase (iv administration of igiv-c 10% treatment), and sc phase (sc administration of igsc 20%). subjects, depending on their current igg treatment regimen, might be required to enter the run-in phase to receive iv igiv-c 10% treatment (sponsor provided) to achieve an approximately steady-state condition prior to entering the iv phase. they then entered the iv phase to determine the auc profiles of iv infusions of igiv-c 10%. subjects with a qualifying iv igiv-c 10% treatment regimen (on stable igiv-c 10% doses of 300-800 mg/kg) entered the iv phase directly where they will receive igiv-c 10%. in the iv phase, steady-state iv pk assessments, including auc, were to be performed. after completing the iv phase, subjects entered the sc phase to receive weekly sc doses of igsc 20% for at least 24 weeks. the pk profiles of total igg following administration of both iv (igiv-c 10%) administration and sc (igsc 20%) administration were determined and compared after reaching approximate steady-state conditions.

Eligibility criteria:
inclusion criteria: * pre-existing diagnosis of primary immunodeficiency with features of hypogammaglobulinemia requiring igg replacement therapy * no serious bacterial infection within the last 3 months prior to or during screening * currently on igg replacement therapy (via iv or sc infusion) for ≥3 consecutive months. subjects receiving igiv must be receiving a dosage of 300 to 800 mg/kg per infusion * documented (at least once within previous 3 months) igg trough level of ≥500 mg/dl on current igg replacement therapy regimen exclusion criteria: * known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product * history of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where sc therapy would be contraindicated during the study * isolated igg subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy * nephrotic syndrome, and/or a history of acute renal failure and/or severe renal impairment, and/or on dialysis * history (year prior to screening or 2 episodes in lifetime ) of or current diagnosis of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular accident or transient ischemic attack) * acquired medical condition known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/μl \[1.0 x 10\^9/l\]), or human immunodeficiency virus infection/acquired immune deficiency syndrome * known previous infection with or clinical signs and symptoms consistent with current hepatitis b virus or hepatitis c virus infection * non-controlled arterial hypertension (systolic blood pressure \>160 mmhg and/or diastolic blood pressure \>100 mmhg in adult subjects) * receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents, (b) immunomodulators, (c) long-term systemic corticosteroids defined as daily dose \>1 mg of prednisone equivalent/kg/day for\>30 days note: intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. inhaled or topical corticosteroids are allowed.