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

Conditions: Primary Immunodeficiency

Summary: approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered immune globulin subcutaneous (human), 20% caprylate/chromatography purified (igsc 20%) who complete the entire study. this study will include 3 study stages: screening/previous regimen phase, igsc 20% treatment stage 1 (13 igsc 20% weekly doses), and igsc 20% treatment stage 2 (39 igsc 20% weekly doses). a total of 52 doses of igsc 20% will be administered with a final follow-up visit 1 week after the last dose at week 53. subjects/caregivers will be trained on self-administration of igsc 20% by the clinical site personnel.

this is a prospective, multi-center, open-label, single-arm, efficacy, pk, safety and tolerability study of igsc 20% in subjects with pi. approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered igsc 20% who complete the entire study. this study will include 3 study stages: screening/previous regimen phase, igsc 20% treatment stage 1 (13 igsc 20% weekly doses), and igsc 20% treatment stage 2 (39 igsc 20% weekly doses). previous regimen phase: subjects will be infused with their current ongoing ("previous regimen") intravenous immune globulin/subcutaneous immune globulin (ivig/scig) regimen (piv/psc) in the clinic to obtain 2 trough immunoglobulin g (igg) levels (obtained prior to each piv/psc infusion) on each subject's "previous regimen". 20% igsc treatment stage 1: the first dose of igsc 20% will be administered at the clinical site immediately after baseline assessments are complete (sc#1). all subjects will receive 13 igsc 20% infusions at weekly intervals. igg trough blood levels will be measured at all (except sc#3) study visits all other doses of igsc 20% may be infused at home (once properly trained) or in the clinic. the treatment stage 1 dose will continue into igsc 20% treatment stage 2. igsc 20% treatment stage 2: the igsc 20% dose (mg/kg) will remain constant with no dose adjustment permitted in this phase, unless it is absolutely medically necessary. while all subjects will have a sc#17 clinic visit and standard assessments, serial pharmacokinetics (pk) sampling will only be performed in a subset of adult subjects:

Eligibility criteria:
inclusion criteria: * pre-existing diagnosis of pi with features of hypogammaglobulinemia requiring igg replacement therapy * no serious bacterial infection within the 3 months prior to screening and has no serious bacterial infections (sbis) up to the time of the baseline visit * currently on igg replacement therapy (stable regimen \[dose and dosing interval\] via iv or sc infusion) for ≥ 3 consecutive months at a dosage of at least 200 mg/kg per infusion * documented (within previous 3 months) of an igg trough level of ≥ 500 mg/dl on current igg replacement therapy regimen * screening/pre-baseline trough igg levels must be ≥ 500 mg/dl. 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 is on dialysis * known previous infection with or clinical signs and symptoms consistent with current hepatitis b virus or hepatitis c virus infection * history of (year prior to screening or 2 episodes in lifetime) or current diagnosis of deep venous thrombosis or thromboembolism (e.g., 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 * hiv positive by nucleic acid amplification technology based on a screening blood sample * uncontrolled arterial hypertension (adult subjects: systolic blood pressure \> 160 mmhg and/or diastolic blood pressure \> 100 mmhg) * 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.