Efficacy, Pharmacokinetics, Safety, and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency

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:

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.