A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency

Study Overview
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Brief Summary
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This study will compare the blood level of Gamunex in patients. Patients will take it as an injection under the skin or in a vein. The study will compare how safe and tolerable the two methods are in the patients. The patients in this study have a defect in their immune system from a genetic cause.

Detailed Description
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This is an open-label, single-sequence, multi-center trial with subjects previously diagnosed with primary immune deficiency. Subjects will be on IGIV until a steady state is reached at which time PK profiling during the IV phase will occur. Subjects will begin SC administration 1 week following last IV dose and followed for a period of six months. PK profiling in SC phase will occur when subject reaches approximate steady-state on SC administration.

Official Title
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An Open-Label Single-Sequence, Crossover Trial to Evaluate the Pharmacokinetics and Safety of Subcutaneous Gamunex® 10% (Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified) in Subjects With Primary Immunodeficiency

Conditions
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Immunologic Deficiency Syndrome

Intervention / Treatment
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* Biological: Immune Globulin Intravenous (Human)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults and adolescents (age 13-75 inclusive) with a documented and confirmed pre-existing diagnosis of chronic primary immunodeficiency Previously or currently on IgG replacement therapy Documented (within 3 months) plasma IgG level of ≥500 mg/dL on current IgG therapy (IgG level can be obtained at the screening visit if documentation is not available) The medical records for all subjects within the previous 2 years should be available to document previous infections and treatment Exclusion Criteria: Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial The subject has a known adverse reaction to Gamunex or other blood products The subject has a history of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections or other disorders where subcutaneous therapy would be contraindicated The subject has known selective IgA deficiency with the exception of a known selective IgA deficient subject who has no previous documented eventful reaction to products containing IgA The subject is pregnant or lactating The subject has significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (BUN or creatinine more than 2.5 times the upper limit of normal) and/or on dialysis The subject has known substance or prescription drug abuse in the past 12 months The subject has a history of or current diagnosis of deep venous thrombosis The subject has an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000 x 10e6/L), or HIV infection/AIDS The subject is receiving any of the following medications: corticosteroids (long-term daily, >1 mg of prednisone equivalent/kg/day for >30 days) (intermittent courses would not exclude subject); immunosuppressants; or immunomodulators The subject has non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) The subject has anemia (hemoglobin <10 g/dL) at screening The subject has participated in another clinical trial 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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Immune Globulin Intravenous (Human)<br>Immune Globulin Intravenous (Human), 10%, Caprylate/Chromatography Purified | Biological: Immune Globulin Intravenous (Human)<br>* This trial was an open-label, single-sequence, study. The enrolled subjects received IGIV-C via two routes of administration (IV for 4 -5 weeks and SC for 24 weeks) in order to compare the PK variables, safety and tolerability of SC administration of IGIV-C. Certain subjects required IV IGIV-C dosing during a Run-in Phase (3 - 4 months) for steady-state conditions prior to the IV phase. Subjects received two IV infusions of IGIV (between 200 - 600 mg based on the subject's previous IgG dosing regimen, 3 to 4 weeks apart) until a steady-state was reached at which time PK profiling was performed. Subjects began weekly SC administration (1.37 times the weekly equivalency of each subject's monthly IV dose) 1 week following last IV dose and followed for a period of six months.<br>* Other names: NDC-13353-645-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG) | Geometric least-squares mean of steady-state plasma concentration of total IgG vs. time profile (AUC). | IV Phase (21 or 28 days) at IV Visit #1, pre- and post-dose: 0 hr., 1 hr., and 1, 2, 3, 5, 7, 14, 21, and 28 days; SC Phase at Week #17, pre- and post-dose: 0 hr., and 1, 3, 4, 5, and 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary immune deficiency