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

An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency

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.

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.