Immune Globulin Subcutaenous (Human), 20%

Study Overview
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Brief Summary
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The purpose of the study is to develop a 20% subcutaneous immunoglobulin treatment option for patients with primary immunodeficiency (PID) diseases.

Official Title
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A Clinical Study of Immune Globulin Subcutaneous (Human) (IGSC), 20% for the Evaluation of Efficacy, Safety, and Pharmacokinetics in Subjects With Primary Immunodeficiency Diseases

Conditions
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Primary Immunodeficiency Diseases (PID)

Intervention / Treatment
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* Biological: Immune Globulin Subcutaneous (Human), 20%
* Biological: Immune Globulin Intravenous (Human), 10%
* Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009, and by diagnostic criteria according to Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Clin Immunol 1999; 93:190-197. The diagnosis must be confirmed by the Medical Director prior to enrollment. Subject is 2 years or older at the time of screening Written informed consent is obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures and study product administration Subject has been receiving a consistent dose of IgG over a period of at least 3 months prior to screening at an average minimum dose over that interval equivalent to 300 mg/kg body weight (BW)/4 weeks and a maximum dose equivalent to 1.0 gram/kg BW/4 weeks at a dosing frequency as follows: intravenously (IV) at mean intervals of approximately 3 or 4 weeks or subcutaneously (SC) at mean intervals of approximately 1 or 2 weeks Subject has a serum trough level of IgG > 5 g/L at screening Subject has not had a serious bacterial infection within the 3 months prior to screening Subject is willing and able to comply with the requirements of the protocol Exclusion Criteria: Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2 Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent): Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500 /mm3) Subject has creatinine clearance (CLcr) value that is < 60% of normal for age and gender Subject has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia Subject has abnormal protein loss (protein losing enteropathy, nephrotic syndrome) Subject has anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti IgA antibodies Subject is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous therapy Subject has total protein >9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia Women of childbearing potential meeting any one of the following criteria subject presents with a positive pregnancy test subject is breast feeding subject intends to begin nursing during the course of the study subject does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study Subject has participated in another clinical study and has been exposed to an investigational product (IP) or device within 30 days prior to study enrollment (exception: treatment with immunoglobulin pre-study) Subject is scheduled to participate in another (non-Baxter) non-observational (interventional) clinical study involving an IP or device during the course of the study Subject has severe dermatitis that would preclude adequate sites for safe product administration

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epoch 1 (intravenous pre-study treatment) + Epoch 2<br>Study Epoch 1 (13 weeks): treatment with KIOVIG (once every 3 or 4 weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents) | Biological: Immune Globulin Subcutaneous (Human), 20%<br>* Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects)<br>* Other names: 20%;Biological: Immune Globulin Intravenous (Human), 10%<br>* Intravenous infusion (regulated via a pump)<br>* Other names: KIOVIG (trademark in Europe);|
| Experimental: Epoch 1 (subcutaneous pre-study treatment) + Epoch 2<br>Study Epoch 1 (12 weeks): treatment with SUBCUVIA (once every week or once every two weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents) | Biological: Immune Globulin Subcutaneous (Human), 20%<br>* Subcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects)<br>* Other names: 20%;Biological: Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)<br>* Subcutaneous infusion (regulated via a pump)<br>* Other names: SUBCUVIA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute serious bacterial infection rate defined as the mean number of acute serious bacterial infections per subject per year in the intent-to-treat population | Acute serious bacterial infections will include bacteremia / sepsis, bacterial meningitis, osteomyelitis / septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Serious Acute Bacterial Infections | 1 year |