Pharmacokinetics, Efficacy, and Safety Study of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)

Study Overview
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Brief Summary
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This is a Phase III, multicenter, open-label study of RI-002 administered as an intravenous infusion of RI-002 (IGIV) every 21 or 28 days in approximately 60 subjects with Primary Immunodeficiency Diseases (PIDD).

Detailed Description
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Primary immunodeficiency diseases (PIDDs) are genetically determined disorders of the immune system resulting in greatly enhanced susceptibility to infectious disease, autoimmunity and malignancy. As most subjects with PIDDs present with infections, the differential diagnosis and initial investigations for an underlying immune defect are typically guided by the clinical presentation. In subjects with PIDDs, individual infections are not necessarily more severe than those that occur in a normal host. Rather, the clinical features suggestive of an immune defect may be the recurring and/or chronic nature of infections with common pathogens that may result in end organ damage, such as bronchiectasis. Several immune globulin products have already been approved by the FDA.

Official Title
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An Open Label, Multicenter, Study to Evaluate the Pharmacokinetics, Efficacy and Safety of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)

Conditions
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Primary Immune Deficiency Disorder

Intervention / Treatment
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* Biological: RI-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible to participate in this study, the subjects must meet the following criteria: Signed a written informed consent or a specific assent form for minors. Have a diagnosis of primary immunodeficiency disease. Be ≥ 2 years and ≤ 75 years. Have body weight ≥ 12 kg at screening. Have been receiving IGIV at a dose that has not been changed by >50% of the mean dose on a mg/kg basis for at least 3 months prior to study entry and have maintained a trough serum Immunoglobulin G (IgG) level ≥ 500 mg/dL on the previous 2 assessments prior to receiving RI 002. The trough level must be at least 300 mg/dL above the pre-treatment serum IgG level. For female subjects, be of non-childbearing potential or have a negative pregnancy test prior to study start and be deemed not at risk of becoming pregnant by adherence to a reliable contraceptive method for the duration of the study. Exclusion Criteria: Subjects must be excluded if they meet any of the following criteria: Have a known hypersensitivity to immunoglobulin or any excipient in RI-002. Have a history of a severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product. Have a specific Immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA. Have uncompensated hemodynamically significant congenital or other heart disease. Have a medical condition that is known to cause secondary immune deficiency. Have a significant T-cell deficiency or deficiency of granulocyte number or function. Have significant renal impairment or have a history of acute renal failure. Have abnormal liver function. Be receiving chronic anti-coagulation therapy. Have a history of deep vein thrombosis (DVT), thrombotic or thrombo-embolic event, or are at increased risk for thrombotic events. Current daily use of the following medications: corticosteroids (> 7.5 mg (or equivalent dose on a mg/kg basis) of prednisone equivalent per day for > 30 days) immunomodulatory drugs immunosuppressive drugs (excluding topical pimecrolimus (Elidel) and tacrolimus (Protopic)) Administration of a hyperimmune or specialty high titer immunoglobulin product. Have uncontrollable arterial hypertension. Have a history of hemolysis or positive Coombs test while undergoing treatment with IGIV therapy. Be morbidly obese as indicated by a Body Mass Index (BMI) ≥ 40 Have received any blood product (other than Immunoglobulin G) within 3 months prior to screening. Have received any Respiratory Syncytial Virus (RSV) specific products, including palivizumab (Synagis®) within 3 months prior to screening. Have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months. Have any condition or abnormal laboratory assessment judged by the investigator to preclude participation in the study. Are currently pregnant or nursing. Have hepatitis A, B, or C.

Ages Eligible for Study
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Minimum Age: 2 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RI-002 Treatment<br>Drug: RI-002 Dose: 300-800 mg/kg infusion Frequency: Once every 3 to 4 Weeks | Biological: RI-002<br>* Immune Globulin Intravenous (IGIV)<br>* Other names: Immune Globulin (Human);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008)) | The primary objective of this study was to demonstrate that RI-002 (IGIV) reduces the frequency of serious bacterial infections (SBIs), as defined by the Diagnostic Criteria for Serious Infection Types guideline, in subjects with primary humoral immunodeficiency. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All Infections (Serious and Non-serious) |  | Up to 1 Year | 
| Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost |  | Up to 1 year | 
| Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year |  | Up to 1 year | 
| Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits |  | Up to 1 year | 
| Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year |  | Up to 1 year | 
| Time to Resolution of Infections - Duration Per Infection |  | Up to 1 year | 
| Time to Resolution of Infections - Infection Days Per Subject |  | Up to 1 year | 
| Number of Hospitalizations Due to Infections |  | Up to 1 year | 
| Number of Hospitalizations Due to Infections - Per Subject-Year |  | Up to 1 year | 
| Days of Hospitalization Due to Infections |  | Up to 1 year | 
| Days of Hospitalization Due to Infections - Per Subject-Year |  | Up to 1 year | 
| Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) | Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined | Up to 1 year | 
| Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year | Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined, per subject-year of treatment with RI-002 | Up to 1 year | 
| Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections | The relationship between trough IgG concentrations and the number of infections of any kind/seriousness was evaluated using Pearson linear correlation coefficients using forward analysis (outcomes after infusion) and backward analysis (outcomes prior to infusion; outcomes post last infusion were excluded) | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - IgG | Summary of trough total IgG concentration prior to specified infusion | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B | Summary of trough antibody concentrations prior to specified infusion for Haemophilus influenzae type B | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) | Summary of trough antibody concentrations prior to specified infusion for Respiratory Syncytial Virus (RSV) | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Tetanus | Summary of trough antibody concentrations prior to specified infusion for Tetanus | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 1 | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 3 | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 4 | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 5 | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 6B | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 7F | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 9V | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 14 | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 18C | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19A | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19F | Up to 1 year | 
| Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F | Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 23F | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PIDD, PID, humoral immunity, antibody deficiency