A Clinical Study of Intravenous Immunoglobulin

Study Overview
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Brief Summary
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The purpose of this study is to measure the pharmacokinetics, efficacy and safety of Immune Globulin Intravenous (Human) [IGIV], 5% Solution Omr-IgG-am™ in patients with primary immunodeficiency diseases.

Detailed Description
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This is an open label, single-arm, prospective, multi-center, uncontrolled Phase III clinical study to evaluate the efficacy, pharmacokinetics and safety of Omr-IgG-am™ in patients with primary immunodeficiency diseases. Approximately 50 subjects will be enrolled for 16 Months: screening- 1 month treatment-12 months follow-up-3 months Subjects will be infused every 21 to 28 days according to their previous IVIG treatment schedule. Subjects treated every 28 days will receive 13 study IGIV infusions. Subjects treated every 21 days will receive 17 study IGIV infusions. We will record the incidence of acute infections, especially acute serious bacterial infections, during the year each subjet is on study. We will record the incidence of adverse events that occur during each infusion and up to 48 hours after each infusion. At the time the study is explained to the subjects, each investigator will ask all subjects whose body weight is above 37 kg (or greater as defined by local standards) about their willingness to participate in the pharmacokinetic (PK) portion of the study. This will involve 4 additional visits after the 5th or 6th study IGIV infusion in order to draw blood samples for analysis.

Official Title
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A Clinical Study of Immune Globulin Intravenous (Human) Omr-IgG-am IGIV in Subjects With Primary Immune Deficiency Diseases

Conditions
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Immunologic Deficiency Syndromes

Intervention / Treatment
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* Drug: Immune Globulin Intravenous (Human) Omr-IgG-am IGIV


Participation Criteria
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Eligibility Criteria
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The following list is incomplete. A complete list is in the protocol. Inclusion Criteria: Ages 3 to 75 years and weigh at least 27 kg. Confirmed clinical diagnosis of a Primary Immune Deficiency disease including hypogammaglobulinemia, preferably with documented antibody deficiency, or agammaglobulinemia. Has been receiving licensed IGIV for at least 3 months prior to this study. Trough IgG levels, dose of IGIV, and treatment intervals for the last 2 consecutive licensed IGIV treatments must be documented. The subject or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form. The subject or legal representative has signed the HIPAA declaration. Exclusion Criteria: Subjects with isolated IgG subclass deficiency or specific antibody deficiency without hypogammaglobulinemia will not be eligible. The subject has a history of hypersensitivity or persistent or repeated adverse reactions to human immunoglobulin. The subject has selective IgA deficiency, history of reaction to products containing IgA, or is known to have antibodies to IgA. The subject is currently participating, or has participated within the previous 30 days, in another clinical study of an investigational product or device. The subject is pregnant or is nursing. Women of childbearing potential must agree to using a method of contraception. The subject has had an acute bacterial infection within 28 days of screening. The subject is seropositive for any of the following at screening: Antibodies to HIV 1&2 Antibodies to HCV HbsAg The subject, at screening, has alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal. The subject has severe renal impairment. The subject has a history of DVT, thrombotic or thrombic complications of IGIV therapy. The subject suffers from any acute or chronic medical condition that, in the opinion of the investigator, may interfere with the conduct of the study. The subject has an acquired medical condition known to cause secondary immune deficiency or otherwise increase the subject's risk of infection.

Ages Eligible for Study
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Minimum Age: 3 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Immune Globulin<br>Subjects with primary humoral immunodeficiency | Drug: Immune Globulin Intravenous (Human) Omr-IgG-am IGIV<br>* IGIV infusions of 300-900 mg/kg every 3 or 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute serious bacterial infections | Acute serious bacterial infections are defined in The FDA(CBER) Guidance for industry for studies of IGIV to support marketing of IGIV as replacement therapy for primary humoral immunodeficiency (June, 2008). | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of hospitalizations and days of hospitalization per subject per year for PID related infections |  | during treatment with study drug-1 year | 
| The incidence of infections other than acute serious bacterial infections |  | during treatment with study drug-1 year | 
| The number of days lost from work/school/usual activities |  | during treatment with study drug-1 year | 
| The number of days of antibiotic therapy (prophylactic and treatment) |  | during treatment with study drug-1 year | 
| Pharmacokinetic parameters of IgG subclasses and specific antibodies will be determined in at least 20 patients: AUC0-t, Cmax, Tmax, t1/2, Vd and elimination rate constants. |  | after 5th or 6th study infusion | 
| Trough levels of IgG subclasses and specific antibodies will be estimated for each subject in the pharmacokinetic study at defined intervals. |  | Months 0, 5, 9, 12 | 
| The number of patients whose trough IgG levels fall below the target of 500 mg/dL at any time will be recorded. |  | one year | 
| All adverse events that occur during the study regardless of the investigator's assessment of the relationship to the investigational product. |  | one year | 
| Laboratory assessments on blood and urine samples including direct antiglobulin (Coomb's) tests. |  | one year | 
| Markers of blood borne virus infections at baseline and up to 3 months after the last infusion i.e. HIV (serology), HCV (serology and NAT), HBV (HbsAg). |  | Months -1, 14, 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deficiency Syndromes, Antibody, Antibody Deficiency Syndrome, Bruton's agammaglobulinemia, Common Variable Immune Deficiency, Hyper IgM syndromes