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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ADMA Biologics, Inc.
ClinicalTrials.gov Identifier:
NCT01814800
First received: March 6, 2013
Last updated: August 10, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
Primary Immune Deficiency Disorder
Biological: RI-002
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by ADMA Biologics, Inc.:

Primary Outcome Measures:
  • Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008)) [ Time Frame: One year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of All Infections (Serious and Non-serious) [ Time Frame: Up to 1 Year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Time to Resolution of Infections - Duration Per Infection [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Time to Resolution of Infections - Infection Days Per Subject [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Number of Hospitalizations Due to Infections [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Number of Hospitalizations Due to Infections - Per Subject-Year [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Days of Hospitalization Due to Infections [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Days of Hospitalization Due to Infections - Per Subject-Year [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined

  • Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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

  • Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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)

  • Trough Total IgG and Specific Antibody Levels - IgG [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough total IgG concentration prior to specified infusion

  • Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Haemophilus influenzae type B

  • Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Respiratory Syncytial Virus (RSV)

  • Trough Total IgG and Specific Antibody Levels - Tetanus [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Tetanus

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 1

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 3

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 4

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 5

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 6B

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 7F

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 9V

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 14

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 18C

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19A

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19F

  • Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 23F


Enrollment: 59
Study Start Date: February 2014
Study Completion Date: January 2015
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RI-002 Treatment
Drug: RI-002 Dose: 300-800 mg/kg infusion Frequency: Once every 3 to 4 Weeks
Biological: RI-002
Immune Globulin Intravenous (IGIV)
Other Name: Immune Globulin (Human)

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

Ages Eligible for Study:   2 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01814800

Locations
United States, Colorado
IMMUNOe Health Centers
Cenntennial, Colorado, United States, 80112
United States, Florida
Allergy Associates of the Palm Beaches, P.A.
North Palm Beach, Florida, United States, 33408
United States, Georgia
Family Allergy Center, PC
Atlanta, Georgia, United States, 30342
United States, Indiana
The South Bend Clinic, LLP
South Bend, Indiana, United States, 46617
United States, Nebraska
Asthma & Immunology Associates
Omaha, Nebraska, United States, 68124
United States, New York
Mount Sinai School of Medicine
NY, New York, United States, 10029
United States, Texas
Dallas Immunology Research
Dallas, Texas, United States, 75230
AARA Research Center
Dallas, Texas, United States, 75231
Baylor Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
ADMA Biologics, Inc.
Investigators
Study Director: James Mond, M.D., Ph.D. ADMA Biologics, Inc.
  More Information

Responsible Party: ADMA Biologics, Inc.
ClinicalTrials.gov Identifier: NCT01814800     History of Changes
Other Study ID Numbers: ADMA-003 
Study First Received: March 6, 2013
Results First Received: December 15, 2015
Last Updated: August 10, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by ADMA Biologics, Inc.:
PIDD, PID, humoral immunity, antibody deficiency

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016