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

Primary Purpose

Primary Immune Deficiency

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Human Normal Immunoglobulin for Subcutaneous Administration
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immune Deficiency focused on measuring Immune globulin subcutaneous, SCIG, Primary immunodeficiency, PID

Eligibility Criteria

2 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Study Site
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IgPro20

Arm Description

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.

Outcomes

Primary Outcome Measures

Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
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)
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)
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)
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
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)
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
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
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
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
Total number of days of hospitalization due to infections for the specified analysis population
Use of Antibiotics for Infection Prophylaxis and Treatment
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
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
Tmax at Steady State
Timepoint of maximum concentration (Cmax)

Full Information

First Posted
December 22, 2006
Last Updated
December 16, 2012
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT00419341
Brief Title
Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy
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)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immune Deficiency
Keywords
Immune globulin subcutaneous, SCIG, Primary immunodeficiency, PID

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IgPro20
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Human Normal Immunoglobulin for Subcutaneous Administration
Other Intervention Name(s)
Hizentra
Primary Outcome Measure Information:
Title
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
Description
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]).
Time Frame
Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
Secondary Outcome Measure Information:
Title
Annualized Rate of Clinically Documented SBIs (ITT Population)
Description
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.
Time Frame
For the duration of the study, up to 15 months
Title
Annualized Rate of Clinically Documented SBIs (PPE Population)
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Annualized Rate of Infection Episodes
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to completion visit)
Title
Number of Infection Episodes (Serious and Non-serious)
Description
Total number of infections for the specified analysis population
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Description
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
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Annualized Rate of Hospitalization Due to Infection
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Number of Days of Hospitalization Due to Infections
Description
Total number of days of hospitalization due to infections for the specified analysis population
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Use of Antibiotics for Infection Prophylaxis and Treatment
Description
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.
Time Frame
Efficacy period: up to 12 months (week 13 to the completion visit)
Title
Total Serum IgG Trough Levels
Description
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Time Frame
Every 4 weeks, throughout the 12-month efficacy period
Title
Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time Frame
Week 28 ± 1 week of the treatment period
Title
Tmax at Steady State
Description
Timepoint of maximum concentration (Cmax)
Time Frame
Week 28 ± 1 week of the treatment period
Other Pre-specified Outcome Measures:
Title
Minimum Concentration (Cmin) of Total Serum IgG at Steady State
Time Frame
Week 28 ± 1 week of the treatment period
Title
Rate of All AEs by Relatedness and Seriousness
Description
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.
Time Frame
For the duration of the study, up to 15 months
Title
Rate of Mild, Moderate, or Severe Local Reactions
Description
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.
Time Frame
For the duration of the study, up to 15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard L. Wasserman, MD, PhD
Organizational Affiliation
Dallas Allergy Immunology and Medical City Children's Hospital,
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Study Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Study Site
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Study Site
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Study Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Study Site
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Study Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Study Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Study Site
City
St.Louis
State/Province
Missouri
ZIP/Postal Code
63104-1095
Country
United States
Facility Name
Study Site
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Study Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Study Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20454851
Citation
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.
Results Reference
result
PubMed Identifier
21553933
Citation
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.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/20454851
Description
Related Info
URL
http://www.cslbehring.com/clinical-trials/contact-us.htm?registryRefNum=NCT00419341&registryName=ctgov
Description
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Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

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