Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT00419341
First received: December 22, 2006
Last updated: December 16, 2012
Last verified: December 2012
  Purpose

The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).


Condition Intervention Phase
Primary Immune Deficiency
Biological: Human Normal Immunoglobulin for Subcutaneous Administration
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: A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population) [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]

    The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.

    Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.


  • Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG) [ Time Frame: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment ] [ Designated as safety issue: No ]
    Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).


Secondary Outcome Measures:
  • Annualized Rate of Clinically Documented SBIs (ITT Population) [ Time Frame: For the duration of the study, up to 15 months ] [ Designated as safety issue: No ]

    The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days.

    Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.


  • Annualized Rate of Clinically Documented SBIs (PPE Population) [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]

    The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.

    Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.


  • Annualized Rate of Infection Episodes [ Time Frame: Efficacy period: up to 12 months (week 13 to completion visit) ] [ Designated as safety issue: No ]
    The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

  • Number of Infection Episodes (Serious and Non-serious) [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    Total number of infections for the specified analysis population

  • Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

  • Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population

  • Annualized Rate of Hospitalization Due to Infection [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

  • Number of Days of Hospitalization Due to Infections [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    Total number of days of hospitalization due to infections for the specified analysis population

  • Use of Antibiotics for Infection Prophylaxis and Treatment [ Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit) ] [ Designated as safety issue: No ]
    Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.

  • Total Serum IgG Trough Levels [ Time Frame: Every 4 weeks, throughout the 12-month efficacy period ] [ Designated as safety issue: No ]
    The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.

  • Maximum Concentration (Cmax) of Total Serum IgG at Steady State [ Time Frame: Week 28 ± 1 week of the treatment period ] [ Designated as safety issue: No ]
  • Tmax at Steady State [ Time Frame: Week 28 ± 1 week of the treatment period ] [ Designated as safety issue: No ]
    Timepoint of maximum concentration (Cmax)


Other Outcome Measures:
  • Minimum Concentration (Cmin) of Total Serum IgG at Steady State [ Time Frame: Week 28 ± 1 week of the treatment period ] [ Designated as safety issue: No ]
  • Rate of All AEs by Relatedness and Seriousness [ Time Frame: For the duration of the study, up to 15 months ] [ Designated as safety issue: Yes ]
    The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.

  • Rate of Mild, Moderate, or Severe Local Reactions [ Time Frame: For the duration of the study, up to 15 months ] [ Designated as safety issue: Yes ]

    In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain.

    Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.



Enrollment: 49
Study Start Date: November 2006
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IgPro20
Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator.
Biological: Human Normal Immunoglobulin for Subcutaneous Administration
Other Name: Hizentra

Detailed Description:

The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.

  Eligibility

Ages Eligible for Study:   2 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged 2 to 75 years
  • Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)
  • Written informed consent

Exclusion Criteria:

  • Newly diagnosed PID
  • Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)
  • Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
  • Known hyperprolinemia
  • Hypoalbuminemia, protein-losing enteropathies, and any proteinuria
  • Allergic reactions to immunoglobulins or other blood products
  • Known antibodies to Immunoglobulin A (IgA)
  • The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants
  • Female who is pregnant, breast feeding or planning a pregnancy during the course of the study
  • Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment
  • A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV)
  • Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL)
  • Creatinine concentration > 1.5 times the UNL
  • Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial
  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: NCT00419341

Locations
United States, California
Study Site
Los Angeles, California, United States, 90027
Study Site
Los Angeles, California, United States, 90025
United States, Colorado
Study Site
Centennial, Colorado, United States, 80112
United States, Florida
Study Site
North Palm Beach, Florida, United States, 33408
United States, Georgia
Study Site
Atlanta, Georgia, United States, 30322
United States, Indiana
Study Site
Fort Wayne, Indiana, United States, 46815
Study Site
Indianapolis, Indiana, United States, 46202
United States, Iowa
Study Site
Iowa City, Iowa, United States, 52242
United States, Missouri
Study Site
St.Louis, Missouri, United States, 63104-1095
United States, New Jersey
Study Site
Newark, New Jersey, United States, 07103
United States, New York
Study Site
New York, New York, United States, 10029
United States, Pennsylvania
Study Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Study Site
Dallas, Texas, United States, 75230
Sponsors and Collaborators
CSL Behring
Investigators
Principal Investigator: Richard L. Wasserman, MD, PhD Dallas Allergy Immunology and Medical City Children's Hospital,
  More Information

Additional Information:
Publications:
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT00419341     History of Changes
Other Study ID Numbers: ZLB04_009CR, 1458
Study First Received: December 22, 2006
Results First Received: December 16, 2012
Last Updated: December 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by CSL Behring:
Immune globulin subcutaneous
SCIG
Primary immunodeficiency
PID

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014