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

ADMA Biologics, Inc.59 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immune Deficiency Disorder

Interventions

RI-002BIOLOGICAL

Immune Globulin Intravenous (IGIV)

Eligibility

Sex: ALLMin age: 2 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (9)

IMMUNOe Health Centers

Cenntennial, Colorado, United States

Allergy Associates of the Palm Beaches, P.A.

North Palm Beach, Florida, United States

Family Allergy Center, PC

Atlanta, Georgia, United States

The South Bend Clinic, LLP

Outcomes

Primary Outcomes

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.

Time frame: One year

Secondary Outcomes

Incidence of All Infections (Serious and Non-serious)

Time frame: Up to 1 Year

Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost

Time frame: Up to 1 year

Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year

Time frame: Up to 1 year

Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits

Time frame: Up to 1 year

Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year

Time frame: Up to 1 year

Time to Resolution of Infections - Duration Per Infection

Time frame: Up to 1 year

Time to Resolution of Infections - Infection Days Per Subject

Time frame: Up to 1 year

Number of Hospitalizations Due to Infections

Time frame: Up to 1 year

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

South Bend, Indiana, United States

Asthma & Immunology Associates

Omaha, Nebraska, United States

Mount Sinai School of Medicine

New York, New York, United States

Dallas Immunology Research

Dallas, Texas, United States

AARA Research Center

Dallas, Texas, United States

Baylor Texas Children's Hospital

Houston, Texas, United States

Number of Hospitalizations Due to Infections - Per Subject-Year

Time frame: Up to 1 year

Days of Hospitalization Due to Infections

Time frame: Up to 1 year

Days of Hospitalization Due to Infections - Per Subject-Year

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: Up to 1 year

Trough Total IgG and Specific Antibody Levels - IgG

Summary of trough total IgG concentration prior to specified infusion

Time frame: 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

Time frame: 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)

Time frame: Up to 1 year

Trough Total IgG and Specific Antibody Levels - Tetanus

Summary of trough antibody concentrations prior to specified infusion for Tetanus

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Up to 1 year