- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00419341
Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90025
- Study site
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Los Angeles, California, United States, 90027
- Study site
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Colorado
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Centennial, Colorado, United States, 80112
- Study site
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Florida
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North Palm Beach, Florida, United States, 33408
- Study site
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Georgia
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Atlanta, Georgia, United States, 30322
- Study site
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Indiana
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Fort Wayne, Indiana, United States, 46815
- Study site
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Indianapolis, Indiana, United States, 46202
- Study site
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Iowa
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Iowa City, Iowa, United States, 52242
- Study site
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Missouri
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St.Louis, Missouri, United States, 63104-1095
- Study site
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New Jersey
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Newark, New Jersey, United States, 07103
- Study site
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New York
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New York, New York, United States, 10029
- Study site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Study site
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Texas
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Dallas, Texas, United States, 75230
- Study site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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)
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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)
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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
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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]).
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Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annualized Rate of Clinically Documented SBIs (ITT Population)
Time Frame: For the duration of the study, up to 15 months
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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
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Annualized Rate of Clinically Documented SBIs (PPE Population)
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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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)
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Annualized Rate of Infection Episodes
Time Frame: Efficacy period: up to 12 months (week 13 to completion visit)
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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.
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Efficacy period: up to 12 months (week 13 to completion visit)
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Number of Infection Episodes (Serious and Non-serious)
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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Total number of infections for the specified analysis population
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Efficacy period: up to 12 months (week 13 to the completion visit)
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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)
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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.
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Efficacy period: up to 12 months (week 13 to the completion visit)
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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)
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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
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Efficacy period: up to 12 months (week 13 to the completion visit)
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Annualized Rate of Hospitalization Due to Infection
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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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.
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Efficacy period: up to 12 months (week 13 to the completion visit)
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Number of Days of Hospitalization Due to Infections
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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Total number of days of hospitalization due to infections for the specified analysis population
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Efficacy period: up to 12 months (week 13 to the completion visit)
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Use of Antibiotics for Infection Prophylaxis and Treatment
Time Frame: Efficacy period: up to 12 months (week 13 to the completion visit)
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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.
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Efficacy period: up to 12 months (week 13 to the completion visit)
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Total Serum IgG Trough Levels
Time Frame: Every 4 weeks, throughout the 12-month efficacy period
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The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
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Every 4 weeks, throughout the 12-month efficacy period
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Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
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Week 28 ± 1 week of the treatment period
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Tmax at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
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Timepoint of maximum concentration (Cmax)
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Week 28 ± 1 week of the treatment period
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Minimum Concentration (Cmin) of Total Serum IgG at Steady State
Time Frame: Week 28 ± 1 week of the treatment period
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Week 28 ± 1 week of the treatment period
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Rate of All AEs by Relatedness and Seriousness
Time Frame: For the duration of the study, up to 15 months
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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.
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For the duration of the study, up to 15 months
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Rate of Mild, Moderate, or Severe Local Reactions
Time Frame: For the duration of the study, up to 15 months
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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
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Richard L. Wasserman, MD, PhD, Dallas Allergy Immunology and Medical City Children's Hospital,
Publications and helpful links
General Publications
- Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, Zenker O, Orange JS. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.
- Wasserman RL, Melamed I, Nelson RP Jr, Knutsen AP, Fasano MB, Stein MR, Rojavin MA, Church JA. Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011 Jun;50(6):405-14. doi: 10.2165/11587030-000000000-00000.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZLB04_009CR
- 1458 (CSL Behring)
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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