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

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).

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.

Eligibility Criteria:
Inclusion Criteria:

To be eligible to participate in this study, the subjects must meet the following criteria:

1. Signed a written informed consent or a specific assent form for minors.
2. Have a diagnosis of primary immunodeficiency disease.
3. Be ≥ 2 years and ≤ 75 years.
4. Have body weight ≥ 12 kg at screening.
5. 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.
6. 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:

1. Have a known hypersensitivity to immunoglobulin or any excipient in RI-002.
2. Have a history of a severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product.
3. Have a specific Immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA.
4. Have uncompensated hemodynamically significant congenital or other heart disease.
5. Have a medical condition that is known to cause secondary immune deficiency.
6. Have a significant T-cell deficiency or deficiency of granulocyte number or function.
7. Have significant renal impairment or have a history of acute renal failure.
8. Have abnormal liver function.
9. Be receiving chronic anti-coagulation therapy.
10. Have a history of deep vein thrombosis (DVT), thrombotic or thrombo-embolic event, or are at increased risk for thrombotic events.
11. 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))
12. Administration of a hyperimmune or specialty high titer immunoglobulin product.
13. Have uncontrollable arterial hypertension.
14. Have a history of hemolysis or positive Coombs test while undergoing treatment with IGIV therapy.
15. Be morbidly obese as indicated by a Body Mass Index (BMI) ≥ 40
16. Have received any blood product (other than Immunoglobulin G) within 3 months prior to screening.
17. Have received any Respiratory Syncytial Virus (RSV) specific products, including palivizumab (Synagis®) within 3 months prior to screening.
18. Have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months.
19. Have any condition or abnormal laboratory assessment judged by the investigator to preclude participation in the study.
20. Are currently pregnant or nursing.
21. Have hepatitis A, B, or C.