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

December 16, 2012 updated by: CSL Behring

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)

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

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90025
        • Study site
      • Los Angeles, California, United States, 90027
        • Study site
    • Colorado
      • Centennial, Colorado, United States, 80112
        • Study site
    • Florida
      • North Palm Beach, Florida, United States, 33408
        • Study site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Study site
    • Indiana
      • Fort Wayne, Indiana, United States, 46815
        • Study site
      • Indianapolis, Indiana, United States, 46202
        • Study site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Study site
    • Missouri
      • St.Louis, Missouri, United States, 63104-1095
        • Study site
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Study site
    • New York
      • New York, New York, United States, 10029
        • Study site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Study site
    • Texas
      • Dallas, Texas, United States, 75230
        • Study site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other Names:
  • Hizentra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)

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.

Efficacy period: up to 12 months (week 13 to the completion visit)
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
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]).
Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Rate of Clinically Documented SBIs (ITT Population)
Time Frame: For the duration of the study, up to 15 months

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.

For the duration of the study, up to 15 months
Annualized Rate of Clinically Documented SBIs (PPE Population)
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)

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.

Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Infection Episodes
Time Frame: Efficacy period: up to 12 months (week 13 to completion visit)
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.
Efficacy period: up to 12 months (week 13 to completion visit)
Number of Infection Episodes (Serious and Non-serious)
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Total number of infections for the specified analysis population
Efficacy period: up to 12 months (week 13 to the completion visit)
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)
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.
Efficacy period: up to 12 months (week 13 to the completion visit)
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)
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
Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Hospitalization Due to Infection
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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.
Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days of Hospitalization Due to Infections
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Total number of days of hospitalization due to infections for the specified analysis population
Efficacy period: up to 12 months (week 13 to the completion visit)
Use of Antibiotics for Infection Prophylaxis and Treatment
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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.
Efficacy period: up to 12 months (week 13 to the completion visit)
Total Serum IgG Trough Levels
Time Frame: Every 4 weeks, throughout the 12-month efficacy period
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Every 4 weeks, throughout the 12-month efficacy period
Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
Week 28 ± 1 week of the treatment period
Tmax at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
Timepoint of maximum concentration (Cmax)
Week 28 ± 1 week of the treatment period

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum Concentration (Cmin) of Total Serum IgG at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
Week 28 ± 1 week of the treatment period
Rate of All AEs by Relatedness and Seriousness
Time Frame: For the duration of the study, up to 15 months
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.
For the duration of the study, up to 15 months
Rate of Mild, Moderate, or Severe Local Reactions
Time Frame: For the duration of the study, up to 15 months

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.

For the duration of the study, up to 15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Richard L. Wasserman, MD, PhD, Dallas Allergy Immunology and Medical City Children's Hospital,

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

December 22, 2006

First Submitted That Met QC Criteria

January 5, 2007

First Posted (Estimate)

January 8, 2007

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

December 16, 2012

Last Verified

December 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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