Back to resultsStudy of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
Primary Purpose
Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
Sponsored by
About this trial
This is an interventional treatment trial for Common Variable Immunodeficiency focused on measuring Subcutaneous immune globulin, SCIG
Eligibility Criteria
Inclusion Criteria:
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia
- Chest X-ray or CT scan obtained within 1 year prior to enrolment
Exclusion Criteria:
- Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy
- Ongoing serious bacterial infection at the time of screening
- Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
- Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA
Additional criteria may apply and examination by an investigator is required to determine eligibility.
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IgPro20
Arm Description
Outcomes
Primary Outcome Measures
Total Serum IgG Trough Levels
Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.
Secondary Outcome Measures
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days.
Annual Rate of Infection Episodes
The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Annual Rate of the Number of Days of Hospitalization Due to Infections
The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment
The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00542997
Brief Title
Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
Official Title
A Multicentre Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
CSL Behring
4. Oversight
Data Monitoring Committee
No
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
This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia
Keywords
Subcutaneous immune globulin, SCIG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IgPro20
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
Other Intervention Name(s)
Hizentra, SCIG
Intervention Description
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.
Primary Outcome Measure Information:
Title
Total Serum IgG Trough Levels
Description
Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.
Time Frame
Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)
Secondary Outcome Measure Information:
Title
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)
Description
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Title
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)
Description
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Title
Annual Rate of Infection Episodes
Description
The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Title
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
Description
The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Title
Annual Rate of the Number of Days of Hospitalization Due to Infections
Description
The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Title
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment
Description
The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Time Frame
Efficacy period: week 12 to week 40 after study start or to the completion visit
Other Pre-specified Outcome Measures:
Title
Maximum Concentration (Cmax) of Total Serum IgG
Time Frame
Week 28 (±1week)
Title
Timepoint of Maximum Concentration (Tmax) of Total Serum IgG
Time Frame
Week 28 (±1week)
Title
Area Under the Concentration-Time Curve (AUC_last) of Total Serum IgG
Description
AUC_last = Area under the concentration-time curve until last measured concentration.
Time Frame
Week 28 (±1week)
Title
Area Under the Concentration-Time Curve (AUCτ) of Total Serum IgG
Description
AUCτ = Area under the concentration-time curve during regular dosing interval;
Time Frame
Week 28 (±1week)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia
Chest X-ray or CT scan obtained within 1 year prior to enrolment
Exclusion Criteria:
Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy
Ongoing serious bacterial infection at the time of screening
Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA
Additional criteria may apply and examination by an investigator is required to determine eligibility.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Jolles, MD
Organizational Affiliation
University Hospital of Wales, Cardiff, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study site
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Study site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Study site
City
Düsseldorf
ZIP/Postal Code
40001
Country
Germany
Facility Name
Study site
City
Freiburg
ZIP/Postal Code
79095
Country
Germany
Facility Name
Study site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Study site
City
Leipzig
ZIP/Postal Code
04129
Country
Germany
Facility Name
Study site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Study site
City
Munich
ZIP/Postal Code
80337
Country
Germany
Facility Name
Study site
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Study site
City
Warsaw
ZIP/Postal Code
04-736
Country
Poland
Facility Name
Study site
City
Bucharest
ZIP/Postal Code
020393
Country
Romania
Facility Name
Study site
City
Cluj-Napoca
ZIP/Postal Code
400162
Country
Romania
Facility Name
Study site
City
Timisoara
ZIP/Postal Code
300011
Country
Romania
Facility Name
Study site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Study site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Study site
City
Göteborg
ZIP/Postal Code
41685
Country
Sweden
Facility Name
Study site
City
Berne
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Study site
City
Cardiff
ZIP/Postal Code
CF 14 4XW
Country
United Kingdom
Facility Name
Study site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
21705277
Citation
Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, Belohradsky BH, Wahn V, Neufang-Huber J, Zenker O, Grimbacher B. Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011 Oct;141(1):90-102. doi: 10.1016/j.clim.2011.06.002. Epub 2011 Jun 12.
Results Reference
result
PubMed Identifier
21674136
Citation
Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, Zenker O, Neufang-Hueber J, Belohradsky B. Efficacy and safety of hizentra(R), a new 20% immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. 2011 Oct;31(5):752-61. doi: 10.1007/s10875-011-9557-z. Epub 2011 Jun 15.
Results Reference
result
Links:
URL
http://www.cslbehring.com/clinical-trials/contact-us.htm?registryRefNum=NCT00542997®istryName=ctgov
Description
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Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
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