Clinical trial NCT01814800: Pharmacokinetics, Efficacy, and Safety Study of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)
Official title: An Open Label, Multicenter, Study to Evaluate the Pharmacokinetics, Efficacy and Safety of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immune Deficiency Disorder
Keywords: PIDD, PID, humoral immunity, antibody deficiency
Lead sponsor: ADMA Biologics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-03-20
Enrollment: 59
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Primary outcomes:
measure: Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008))
timeFrame: One year
Secondary outcomes:
measure: Incidence of All Infections (Serious and Non-serious)
timeFrame: Up to 1 Year
measure: Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost
timeFrame: Up to 1 year
measure: Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year
timeFrame: Up to 1 year
measure: Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits
timeFrame: Up to 1 year
measure: Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year
timeFrame: Up to 1 year
measure: Time to Resolution of Infections - Duration Per Infection
timeFrame: Up to 1 year
measure: Time to Resolution of Infections - Infection Days Per Subject
timeFrame: Up to 1 year
measure: Number of Hospitalizations Due to Infections
timeFrame: Up to 1 year
measure: Number of Hospitalizations Due to Infections - Per Subject-Year
timeFrame: Up to 1 year
measure: Days of Hospitalization Due to Infections
timeFrame: Up to 1 year
measure: Days of Hospitalization Due to Infections - Per Subject-Year
timeFrame: Up to 1 year
measure: Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection)
timeFrame: Up to 1 year
measure: Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year
timeFrame: Up to 1 year
measure: Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - IgG
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV)
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Tetanus
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F
timeFrame: Up to 1 year
measure: Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Cenntennial
country: United States
facility: IMMUNOe Health Centers
state: Colorado
city: North Palm Beach
country: United States
facility: Allergy Associates of the Palm Beaches, P.A.
state: Florida
city: Atlanta
country: United States
facility: Family Allergy Center, PC
state: Georgia
city: South Bend
country: United States
facility: The South Bend Clinic, LLP
state: Indiana
city: Omaha
country: United States
facility: Asthma & Immunology Associates
state: Nebraska
city: NY
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Dallas
country: United States
facility: Dallas Immunology Research
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Houston
country: United States
facility: Baylor Texas Children's Hospital
state: Texas
Study officials:
affiliation: ADMA Biologics, Inc.
name: James Mond, M.D., Ph.D.
role: STUDY_DIRECTOR
References: