Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency

Study Overview
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Brief Summary
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The purpose of this open-label study is to evaluate the pharmacokinetics, safety, and tolerability of subcutaneously (SC; under the skin) administered GAMUNEX-C compared to intravenously (IV; through the vein) administered GAMUNEX-C in subjects 2-16 years of age with Primary Immunodeficiency.

Detailed Description
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This study was a multi-center, open-label, single-sequence, crossover study to evaluate the pharmacokinetics (PK), safety and tolerability of SC-administered GAMUNEX-C in pediatric PI subjects (ages 2-16). The study consisted of a Screening Phase, Run-in Phase, two treatment phases (an IV Phase and a SC Phase), and an End of Study/Early Termination (EOS/ET) visit. Run-in phase: 3 - 4 months, IV Phase:   4 - 5 weeks, SC Phase: 12 weeks, and End of Study/Early Termination (EOS/ET) visit: one week after SC Week #12.

Official Title
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An Open-label, Single-sequence, Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Subcutaneous GAMUNEX®-C in Pediatric Subjects With Primary Immunodeficiency

Conditions
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Primary Immunodeficiency

Intervention / Treatment
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* Biological: GAMUNEX-C
* Biological: GAMUNEX-C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2-16 years old, inclusive. Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring immunoglobulin replacement. Currently on IgG replacement therapy with a serum IgG trough concentration of ≥ 500 mg/dL at the Screening Visit. Adequate normal skin to allow for SC infusions. Signs an assent form, if applicable (per Institutional Review Board [IRB] requirements). Parent or legal guardian must sign an informed consent form. Females of childbearing potential must have a negative urine pregnancy test result and must practice an effective form of contraception (which may include abstinence). Exclusion Criteria: History of anaphylaxis or severe systemic response to an immunoglobulin or blood product. History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, recurrent skin infections or other disorders where subcutaneous therapy could be contraindicated. Has a specific antibody deficiency disorder, IgG subclass deficiency, or transient hypogammaglobulinemia of infancy. History of severe adverse reaction to parenteral products containing immunoglobulin A (IgA). Significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (serum creatinine more than 2.5 times the upper limit of normal [ULN] for age and gender) and/or is on dialysis. Known substance or prescription drug abuse in the past 12 months. Acquired medical condition that is known to cause secondary immune deficiency. Receiving any of the following medications: systemic corticosteroids (long term daily, >1 mg of prednisone equivalent/kg/day for >30 days) (intermittent courses would not exclude subject); immunosuppressants (i.e., antimetabolites and systemic calcineurin inhibitors; NOTE: inhaled steroids are allowed); or immunomodulators. Non-controlled arterial hypertension at a level of ≥ the 90th percentile blood pressure (either systolic or diastolic) for age and height (based on http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.pdf ). History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device > 2 years prior to screening are allowed. Currently receiving anti-coagulation therapy. History of Kawasaki disease. Participated in another clinical trial involving exposure to an investigational product or device within 30 days prior to screening (imaging studies without investigative treatments are permitted) or has received any investigational blood product within the previous 3 months. Unable or unwilling to comply with any aspect of the protocol, including blood sampling and completion of the Infusion Site Reactions pages in the SC Infusion Diary. In the opinion of the Investigator the subject may have compliance problems with the protocol and the procedures of the protocol. Pregnant or lactating. Clinical evidence of any significant acute or chronic disease that, in the opinion of the Investigator, may interfere with successful completion of the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum 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
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous GAMUNEX-C<br> | Biological: GAMUNEX-C<br>* GAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Intravenous Administration: 200-600 mg/kg per intravenous infusion every 3-4 weeks<br>|
| Experimental: Subcutaneous GAMUNEX-C<br> | Biological: GAMUNEX-C<br>* GAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Subcutaneous Administration: weekly subcutaneous infusion at a mg/kg dose based on subject's intravenous dose and dosing interval x 1.37 conversion factor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady-state Area Under the Curve (AUC) for Serum Total Immunoglobulin (IgG) | Steady-state area under the curve (AUC): For the IV phase, the mean adjusted AUC was calculated for all 11 subjects, which included subjects on both 3 and 4 week intravenous (IV) dosing schedules and who had sufficient immunoglobulin G (IgG) data. For the SC phase, the mean AUC was calculated for 10 subjects on weekly subcutaneous (SC) administration and who had sufficient IgG data. | 4 to 5 weeks for IV administration; 12 weeks for SC administration | 
| Mean Trough of Serum Total IgG | Mean trough serum total IgG values were calculated for each subject for the IV Phase (IV #1 and IV #2) and the SC phase (SC Weeks #9 and #12, and End of Treatment/Early termination visit). Mean trough concentration values of serum total IgG during the IV and SC phases were calculated based on the IgG population (subjects who received any amount of study drug and had serum total IgG concentration data). | 4 - 5 weeks of IV administration and 12 weeks for SC administration |