Study to Determine the Dose of Recombinant Human Hyaluronidase Needed to Infuse a Full Dose of IGIV Subcutaneously

Phase 1/2 Determination of the Dose of Recominant Human Hyaluronidase (rHuPH20) Required Enabling Up to 600 mg/kg Bodyweight of IGIV, 10% to be Administered Subcutaneously in a Single Infusion Site in Subjects With Primary Immunodeficiency (PID)

The purpose of the study is to determine the feasibility of infusing a full 4-week dose of Immune Globulin Intravenous (Human), 10% in a single subcutaneous site and the amount of recombinant human hyaluronidase needed to infuse that dose with no more than mild local adverse drug reactions.

Inclusion Criteria:

• Written informed consent from either the subject or the subject's legally acceptable representative
• Diagnosis of a PID disorder as defined by World Health Organization criteria1 for which the subject had been receiving a regimen of weekly or biweekly (every-other-week) subcutaneous IgG infusions or IGIV infusions every 21 to 28 days over a period of at least 8 weeks pre-study at an equivalent of a 4-week dose of 300 to 800 mg/kg bodyweight
• Adults/adolescents aged 16 years and older)
• For female subjects of child-bearing age: negative urine pregnancy test result at study entry and agreement to employ adequate birth control measures for the duration of the study

Exclusion Criteria:

• Subjects positive at enrollment for one or more of the following: HBsAg, PCR for HCV, PCR for HIV Type 1
• Subjects with levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
• Subjects with neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3).
• Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender
• Subjects with current history of malignancy
• Subjects with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident)
• Subjects with abnormal protein loss (protein losing enteropathy, nephritic syndrome, severe lung disease)
• Subjects with anemia that in the opinion of the investigator precluded phlebotomy for laboratory studies
• Subjects who had been exposed to any blood or blood product other than an intravenous immunoglobulin (IGIV), SC immunoglobulin (SCIG), immune serum globulin (ISG) preparations, or albumin within the 6 months prior to study entry.
• Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SCIG and/or ISG infusions
• Subjects with IgA deficiency and known anti IgA antibodies
• Subjects who had received antibiotic therapy for the treatment of infection within 7 days prior to enrollment
• Subjects who had participated in another clinical study involving an investigational product or device within 28 days prior to study entry
• Subjects with inability or unwillingness to meet all the requirements of this study
• If female, pregnancy or lactation at time of study entry