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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Primary Immunodeficiency Diseases (PID)

Intervention / Treatment
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* Biological: Recombinant human hyaluronidase + immune globulin intravenous
* Biological: Recombinant human hyaluronidase + immune globulin intravenous


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Tolerability of subcutaneous infusions | Biological: Recombinant human hyaluronidase + immune globulin intravenous<br>* Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered<br>* Other names: rHuPH20 = Recombinant Human Hyaluronidase;|
| Experimental: 2<br>Tolerability of subcutaneous infusions and pharmacokinetics | Biological: Recombinant human hyaluronidase + immune globulin intravenous<br>* IV infusion of IGIV, 10% to determine pharmacokinetics Intervention as in Arm 1: Dose (calculated) of rHuPH20 followed by subcutaneous infusion of IGIV, 10% to determine tolerability: doses of rHuPH20 and IGIV, 10% to be increased, as tolerated and as per protocol, until a full 4-week IgG dose can be administered<br>* Other names: rHuPH20 = Recombinant Human Hyaluronidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to administer, after priming with recombinant human hyaluronidase, at least one half of a 4-week dose (minimum of 200 mg/kg) of IgG in a single infusion site, via the subcutaneous route, with no more than mild local adverse drug reactions. |  | 72 hours |