Back to resultsComparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects
Primary Purpose
Primary Immunodeficiency Diseases (PID)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Immune Globulin Intravenous (Human), 10%
Sponsored by
About this trial
This is an interventional treatment trial for Primary Immunodeficiency Diseases (PID)
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to any study-related procedures and study product administration
- Diagnosis of a PID disorder as defined by World Health Organization criteria (IUIS Scientific Committee, Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999) for which the subject has been receiving a regular regimen of IV immunoglobulin infusions every 21 ± 3 days or 28 ± 3 days or a regular SC immunoglobulin treatment at 1 to 2 week intervals over a period of at least 3 months pre-study at a dose of 300-800 mg/kg BW/4 weeks
- Subjects are aged 2 years or older
- Subjects have a serum trough level of IgG > 4.5 g/L at the last documented determination
- A negative serum pregnancy test for any female subject who is of childbearing potential
- Female subjects of childbearing potential agree to practice birth control measures for the duration of the study
Exclusion Criteria:
- Subjects positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), PCR for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1
- Subjects with levels of alanine amino transferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
- Subjects with neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
- Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender
- Subjects with a malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Subjects with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident)
- Subjects with abnormal protein loss (protein losing enteropathy, nephritic syndrome, severe lung disease)
- Subjects with anemia that would preclude phlebotomy for laboratory studies
- Subjects who received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to study enrollment
- Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin and/or ISG infusions
- Subjects with IgA deficiency and known anti IgA antibodies
- Subjects receiving antibiotic therapy for the treatment of infection within 7 days prior to enrollment
- Subjects participating in another clinical study involving an investigational product or device within 28 days prior to study enrollment
- Subjects with bleeding disorders or who are on anti-coagulation therapy
Sites / Locations
Outcomes
Primary Outcome Measures
Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage
Expressed as (AUC_SC/AUC_IV) * 100
Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)
Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Secondary Outcome Measures
Study Part 1 (IV): Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Study Part 1 (IV): Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Study Part 1 (IV): Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Study Part 1 (IV): Terminal Half-life
Computed from the regression slope in the terminal phase of the model (the slope is biphasic). Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50%during the terminal phase.
Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max)
Time to reach C-max
Study Part 2 (SC): Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Study Part 2 (SC): Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Study Part 3B: Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max)
Time to reach C-max
Study Part 3B: Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Study Part 3B: Area Under the Curve (AUC)
The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 or 28 days for IV administration and 7 days for SC administration). To allow for comparisons between Study Parts 1, 2 and 3b, AUC(0-τ) was standardized for the infusion intervals (3 or 4 weeks vs. 1 week).
Study Part 3B: Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older
Part 1: IgG trough levels measured at each IV infusion day (every 3rd or 4th week depending on schedule/frequency of participants for a total of 12 weeks) Part 2: IgG trough levels measured at weeks 1, 5 and 9 (of a total of 12 weeks) Part 3a: IgG trough levels measured at weeks 1 and 5 (of a total of 6 weeks) Part 3b: IgG trough levels measured at weeks 1, 5, 9 and 12 (of a total of 12 weeks)
Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Trough Levels of Antibody to Hepatitis B in All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Trough Levels of Antibody to Tetanus In All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level
Antibody Titers That Were Below or Above the Protective Titer Level of >1:8 for IV and SC Treatment in Study Parts 1, 2, 3a and 3b. Participants had multiple anti-measles antibody titers measured during the study.
Annual Infection Rates During Treatment
Annual rate of all infections calculated using a Poisson model to account for different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with allowance for overdispersion by deviance method. Point estimates and likelihood-ratio based 95% confidence intervals were provided. Infections as included in analysis comprised all reported AEs that were coded to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of infections and infestations, described as an infection by investigator, or for which anti-infective medication was prescribed.
Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS)
Annual rate of validated acute serious bacterial infections was calculated using a Poisson model to account for the different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with an allowance for overdispersion by the deviance method.
Rate of Temporally Associated AEs Per Infusion
Rate of AEs per infusion defined as the total number of all AEs that begin during infusion or within 72 hours of completion of an infusion ("temporally associated") divided by the total number of infusions.
AEs Deemed/Judged to be Related by the Investigator
Rate of related AEs defined as the total number of AEs determined by the investigator to be related to the study drug that occur at any time during the study divided by the total number of infusions.
Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L)
Frequency of Dose Adjustments Based on IgG Trough Levels <4.5 g/L IgG, if Any, for Each Study Part. Defined/calculated as the number of participants requiring dose adjustments divided by the number of participants, for each respective data set.
Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs
Proportion of Participants Reporting 1 or More Moderate or Severe AEs That Begin During Infusion or Within 72 Hours of Completion of an Infusion.
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Percentage of Infusions Associated With ≥1 AE Related to the Study Drug
Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion
Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Full Information
NCT ID
NCT00546871
First Posted
October 18, 2007
Last Updated
April 29, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT00546871
Brief Title
Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects
Official Title
Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human) 10% (IGIV, 10%) Administered Intravenously or Subcutaneously in Subjects With Primary Immunodeficiency Diseases
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
October 3, 2007 (Actual)
Primary Completion Date
July 1, 2009 (Actual)
Study Completion Date
September 1, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency Diseases (PID)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Immune Globulin Intravenous (Human), 10%
Intervention Description
Intravenous administration in Study Part 1, subcutaneous administration in Study Parts 2 and 3
Primary Outcome Measure Information:
Title
Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage
Description
Expressed as (AUC_SC/AUC_IV) * 100
Time Frame
Week 12 (IV) and week 32 or 33 (SC)
Title
Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
Description
Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Title
Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Title
Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Title
Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Title
Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Title
Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Title
Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Description
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Time Frame
Throughout study (1 year and 9 months)
Secondary Outcome Measure Information:
Title
Study Part 1 (IV): Maximum Plasma Concentration (C-max)
Description
Maximal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Title
Study Part 1 (IV): Minimum Plasma Concentration (C-min)
Description
Minimal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Title
Study Part 1 (IV): Weight-adjusted Clearance
Description
Computed as weight-adjusted dose divided by total AUC
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Title
Study Part 1 (IV): Terminal Half-life
Description
Computed from the regression slope in the terminal phase of the model (the slope is biphasic). Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50%during the terminal phase.
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Title
Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)
Description
Maximal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max)
Description
Time to reach C-max
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 2 (SC): Minimum Plasma Concentration (C-min)
Description
Minimal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 2 (SC): Weight-adjusted Clearance
Description
Computed as weight-adjusted dose divided by total AUC
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 3B: Maximum Plasma Concentration (C-max)
Description
Maximal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max)
Description
Time to reach C-max
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 3B: Minimum Plasma Concentration (C-min)
Description
Minimal immune globulin concentration after infusion
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 3B: Area Under the Curve (AUC)
Description
The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 or 28 days for IV administration and 7 days for SC administration). To allow for comparisons between Study Parts 1, 2 and 3b, AUC(0-τ) was standardized for the infusion intervals (3 or 4 weeks vs. 1 week).
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Study Part 3B: Weight-adjusted Clearance
Description
Computed as weight-adjusted dose divided by total AUC
Time Frame
Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Title
Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older
Description
Part 1: IgG trough levels measured at each IV infusion day (every 3rd or 4th week depending on schedule/frequency of participants for a total of 12 weeks) Part 2: IgG trough levels measured at weeks 1, 5 and 9 (of a total of 12 weeks) Part 3a: IgG trough levels measured at weeks 1 and 5 (of a total of 6 weeks) Part 3b: IgG trough levels measured at weeks 1, 5, 9 and 12 (of a total of 12 weeks)
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Title
Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants
Description
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Title
Trough Levels of Antibody to Hepatitis B in All Study Participants
Description
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Title
Trough Levels of Antibody to Tetanus In All Study Participants
Description
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Title
Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level
Description
Antibody Titers That Were Below or Above the Protective Titer Level of >1:8 for IV and SC Treatment in Study Parts 1, 2, 3a and 3b. Participants had multiple anti-measles antibody titers measured during the study.
Time Frame
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Title
Annual Infection Rates During Treatment
Description
Annual rate of all infections calculated using a Poisson model to account for different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with allowance for overdispersion by deviance method. Point estimates and likelihood-ratio based 95% confidence intervals were provided. Infections as included in analysis comprised all reported AEs that were coded to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of infections and infestations, described as an infection by investigator, or for which anti-infective medication was prescribed.
Time Frame
Throughout the study, 1 year and 9 months
Title
Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS)
Description
Annual rate of validated acute serious bacterial infections was calculated using a Poisson model to account for the different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with an allowance for overdispersion by the deviance method.
Time Frame
Throughout the study, 1 year and 9 months
Title
Rate of Temporally Associated AEs Per Infusion
Description
Rate of AEs per infusion defined as the total number of all AEs that begin during infusion or within 72 hours of completion of an infusion ("temporally associated") divided by the total number of infusions.
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
Title
AEs Deemed/Judged to be Related by the Investigator
Description
Rate of related AEs defined as the total number of AEs determined by the investigator to be related to the study drug that occur at any time during the study divided by the total number of infusions.
Time Frame
Throughout the study period (1 year and 9 months)
Title
Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L)
Description
Frequency of Dose Adjustments Based on IgG Trough Levels <4.5 g/L IgG, if Any, for Each Study Part. Defined/calculated as the number of participants requiring dose adjustments divided by the number of participants, for each respective data set.
Time Frame
Throughout the study period (1 year and 9 months)
Title
Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs
Description
Proportion of Participants Reporting 1 or More Moderate or Severe AEs That Begin During Infusion or Within 72 Hours of Completion of an Infusion.
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
Title
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Time Frame
Throughout entire study (1 year and 9 months)
Title
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Time Frame
Throughout entire study (1 year and 9 months)
Title
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Time Frame
Throughout entire study (1 year and 9 months)
Title
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Time Frame
Throughout entire study (1 year and 9 months)
Title
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Time Frame
Throughout entire study (1 year and 9 months)
Title
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Description
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Time Frame
Throughout entire study (1 year and 9 months)
Title
Percentage of Infusions Associated With ≥1 AE Related to the Study Drug
Time Frame
Throughout the study period (1 year and 9 months)
Title
Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
Title
Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
Title
Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
Title
Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time Frame
During Infusion or Within 72 Hours of Completion of Infusions
10. Eligibility
Sex
All
Minimum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to any study-related procedures and study product administration
Diagnosis of a PID disorder as defined by World Health Organization criteria (IUIS Scientific Committee, Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999) for which the subject has been receiving a regular regimen of IV immunoglobulin infusions every 21 ± 3 days or 28 ± 3 days or a regular SC immunoglobulin treatment at 1 to 2 week intervals over a period of at least 3 months pre-study at a dose of 300-800 mg/kg BW/4 weeks
Subjects are aged 2 years or older
Subjects have a serum trough level of IgG > 4.5 g/L at the last documented determination
A negative serum pregnancy test for any female subject who is of childbearing potential
Female subjects of childbearing potential agree to practice birth control measures for the duration of the study
Exclusion Criteria:
Subjects positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), PCR for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1
Subjects with levels of alanine amino transferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
Subjects with neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender
Subjects with a malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Subjects with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident)
Subjects with abnormal protein loss (protein losing enteropathy, nephritic syndrome, severe lung disease)
Subjects with anemia that would preclude phlebotomy for laboratory studies
Subjects who received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to study enrollment
Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin and/or ISG infusions
Subjects with IgA deficiency and known anti IgA antibodies
Subjects receiving antibiotic therapy for the treatment of infection within 7 days prior to enrollment
Subjects participating in another clinical study involving an investigational product or device within 28 days prior to study enrollment
Subjects with bleeding disorders or who are on anti-coagulation therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Centennial
State/Province
Colorado
Country
United States
City
North Palm Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Galveston
State/Province
Texas
Country
United States
City
Milwaukee
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
9440877
Citation
Neu AM, Warady BA, Furth SL, Lederman HM, Fivush BA. Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium. Adv Perit Dial. 1997;13:297-9.
Results Reference
background
Citation
Leibl H, Engl W, Melamed I, Stein M, Wasserman RL, Berger M, Schiff RI. IGIV-10% Infused Intravenously And Subcutaneously To Subjects With Primary Immunodeficiency Diseases - Comparison Of Pharmacokinetic Properties. Poster presentation at AAAAI 2009.
Results Reference
result
Citation
Schiff RI, Leibl H, Engl W. Pharmacokinetic properties of Gammagard Liquid 10% (KIOVIG) administered intravenously and subcutaneously to patients with primary immunodeficiency diseases. Clin Exp Immunol. 154 (Suppl. 1):132, 2008
Results Reference
result
PubMed Identifier
21424824
Citation
Wasserman RL, Melamed I, Kobrynski L, Strausbaugh SD, Stein MR, Sharkhawy M, Engl W, Leibl H, Sobolevsky L, Gelmont D, Schiff RI, Grossman WJ. Efficacy, safety, and pharmacokinetics of a 10% liquid immune globulin preparation (GAMMAGARD LIQUID, 10%) administered subcutaneously in subjects with primary immunodeficiency disease. J Clin Immunol. 2011 Jun;31(3):323-31. doi: 10.1007/s10875-011-9512-z. Epub 2011 Mar 22.
Results Reference
result
PubMed Identifier
34931880
Citation
Wasserman RL, Gupta S, Stein M, Rabbat CJ, Engl W, Leibl H, Yel L. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases. Immunotherapy. 2022 Mar;14(4):215-224. doi: 10.2217/imt-2021-0256. Epub 2021 Dec 21.
Results Reference
derived
Learn more about this trial
Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects
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