Safety and Efficacy Study of Flebogamma 5% DIF IGIV in Pediatric Subjects

Study Overview
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Brief Summary
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This is a multi-center, open-label study to assess the efficacy and safety of Flebogamma 5% DIF in the pediatric population.

Official Title
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Evaluation of the Efficacy and Safety of Flebogamma 5% DIF [Immune Globulin Intravenous (Human)] for Replacement Therapy in Pediatric Subjects With Primary Immunodeficiency Diseases.

Conditions
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Primary Immune Deficiency Disease

Intervention / Treatment
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* Biological: Flebogamma 5% DIF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is between 2 and 16 years old, of either sex, belonging to any ethnic group, and above a minimum weight of 10 kg (this weight is based on the amount of blood required for testing). The subject has a primary immunodeficiency disease, (e.g., common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome, Wiskott-Aldrich Syndrome). The subject has been receiving licensed IGIV replacement therapy at a dose that has not changed by + 50% of the mean dose on a mg/kg basis for at least 3 months before study entry and has maintained a trough level at least 300 mg/dL above baseline serum IgG levels. Trough levels of IgG, dose of IGIV, and treatment intervals for the last 2 consecutive routine IGIV treatments must be documented for each subject before the first infusion in this study can be administered. If a subject is an adolescent female (> 12 years of age) who is or becomes sexually active, she must have a negative result on a pregnancy test (HCG-based assay). The subject, if old enough (generally 6 years to 16) has signed an informed Child Assent form and the subject's parent or legal guardian has signed an informed consent form, both approved by the Institutional Review Board. Exclusion Criteria: Adult patient (> 17 years old). The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product. The subject is known to be intolerant to any component of the products, such as sorbitol (i.e., intolerance to fructose). The subject has selective IgA deficiency or has demonstrable antibodies to IgA. The subject is currently receiving, or has received, any investigational agent within the prior 3 months. The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV. The adolescent subject is pregnant or is nursing. The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory for pediatric patients of any of the following: ALT AST LDH The subject has a severe pre-existing renal impairment (defined by serum creatinine greater than 2 times the ULN or BUN greater than 2.5 times the ULN for that laboratory, or any subject who is on dialysis) or any history of acute renal failure. The subject has a history of DVT or thrombotic complications of IGIV therapy. The subject suffers from any acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the Investigator, may interfere with the conduct of the study. The subject has an acquired medical condition such as lymphocytic leukemia, chronic or recurrent neutropenia (ANC less than 1000), or AIDS known to cause secondary immune deficiency, or is s/p hematopoetic stem cell transplantation. The subject is receiving the following medication: Systemic corticosteroids (long-term, i.e., not intermittent or burst, daily, > 1 mg of prednisone equivalent/kg/day). Topical steroids (ie- nasal, inhaled for asthma, and/or skin preparations for eczema) are not exclusionary. Immunosuppressive drugs Immunomodulatory drugs The subject has non-controlled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg). The subject has anemia (hemoglobin < 10 g/dL) at screening. The subject and/or parent/legal guardian of the subject is unlikely to adhere to the protocol requirements of the study or is likely to be uncooperative or unable to provide from the patient a storage serum sample at the screening visit. (Please note, a pre-treatment serum sample to be stored at -94° F (-70º C) for possible future testing is absolutely required).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flebogamma 5% DIF<br> | Biological: Flebogamma 5% DIF<br>* Intravenous Immune Globulin (Human)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Bacterial Infections. | Total number of Bacterial pneumonia, bacteremia or sepsis, osteomyelitis/septic arthritis, visceral abscess or bacterial meningitis | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of School/Usual Activities Missed Per Year | Mean Days of school/usual activities missed per subject/year | 12 months | 
| Days of Hospitalization Per Year | Mean Days of hospitalization per subject/year | 12 months | 
| Number of Visits to Physician/ER Room for Acute Problems | Mean Number of visits to physician/ER room for acute problems | 12 months | 
| Other Infections Documented by Fever and Physical Exam or Positive Radiograph. |  | 12 months | 
| Number of Infectious Episodes Per Year | Mean Number of infectious episodes per subject/year | 12 months | 
| Number of Days on Antibiotics (Prophylactic and Therapeutic). | Median Combined number of days on prophylactic and therapeutic antibiotics | 12 months | 
| Number of Adverse Events | Total Number of Adverse Events | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CVID, XLA, hyper IgM syndrome, Wiskott-Aldrich Syndrome