Phase 3
N=49
Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects
Primary Immunodeficiency Diseases (PID)
Bottom Line
View on ClinicalTrials.gov: NCT00546871 ↗Enrolled (actual)
49
Serious AEs
4.1%
Results posted
Aug 2012
Primary outcome: Primary: 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 — 95.2 percent
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Immune Globulin Intravenous (Human), 10% (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jul 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
95.2 | — |
| PRIMARY Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years. |
11.400; 10.100; 11.500; 10.600; 10.100; 10.800 | — |
| PRIMARY 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 |
18.4; 16.3; 29.8; 4.3; 15.9; 2.3 | — |
| PRIMARY 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. |
23.7; 21.1; 33.3; 5.6; 20.6; 2.9 | — |
| PRIMARY 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 |
0.0; 0.00; 18.2; 0.00; 0.00; 0.00 | — |
| PRIMARY Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped |
6.7; 6.2; 4.2; 0.5; 3.1; 0.4 | — |
| PRIMARY Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped |
8.7; 8.0; 4.5; 0.6; 4.0; 0.5 | — |
| PRIMARY Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped |
0.0; 0.0; 3.3; 0.0; 0.0; 0.0 | — |
| SECONDARY Study Part 1 (IV): Maximum Plasma Concentration (C-max) |
22.7 | — |
| SECONDARY Study Part 1 (IV): Minimum Plasma Concentration (C-min) |
10.1 | — |
| SECONDARY Study Part 1 (IV): Weight-adjusted Clearance |
1.36 | — |
| SECONDARY Study Part 1 (IV): Terminal Half-life |
33.1 | — |
| SECONDARY Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max) |
14.5 | — |
| SECONDARY Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max) |
4.8 | — |
| SECONDARY Study Part 2 (SC): Minimum Plasma Concentration (C-min) |
12.5 | — |
| SECONDARY Study Part 2 (SC): Weight-adjusted Clearance |
1.86 | — |
| SECONDARY Study Part 3B: Maximum Plasma Concentration (C-max) |
14.1 | — |
| SECONDARY Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max) |
2.9 | — |
| SECONDARY Study Part 3B: Minimum Plasma Concentration (C-min) |
12.6 | — |
| SECONDARY Study Part 3B: Area Under the Curve (AUC) |
94.6 | — |
| SECONDARY Study Part 3B: Weight-adjusted Clearance |
2.00 | — |
| SECONDARY Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older |
11.800; 10.900; 11.050; 14.000; 11.700; 12.400 | — |
| SECONDARY Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants |
2.790; 2.830; 2.885; 3.150; 3.145; 3.045 | — |
| SECONDARY Trough Levels of Antibody to Hepatitis B in All Study Participants |
239.450; 182.050; 251.150; 282.050; 274.200; 261.850 | — |
| SECONDARY Trough Levels of Antibody to Tetanus In All Study Participants |
2.840; 3.010; 3.500; 3.360; 3.205; 3.520 | — |
| SECONDARY Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level |
0; 654 | — |
| SECONDARY Annual Infection Rates During Treatment |
5.0; 5.2; 5.6; 4.1; 3.5; 4.6 | — |
| SECONDARY Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS) |
0.000; 0.067 | — |
| SECONDARY Rate of Temporally Associated AEs Per Infusion |
0.25; 0.45; 0.00; 0.08; 0.13; 0.08 | — |
| SECONDARY AEs Deemed/Judged to be Related by the Investigator |
0.00; 0.25; 0.00; 0.07; 0.06; 0.08 | — |
| SECONDARY Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L) |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs |
0.43; 0.47; 0.27; 0.36; 0.44; 0.09 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS) |
0; 0; 0; 0; 3; 3 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS) |
0.00; 0.00; 0.00; 0.00; 0.04; 0.04 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages) |
0; 0; 0; 0; 2; 2 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages) |
0.00; 0.00; 0.00; 0.00; 0.05; 0.05 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC) |
0; 0; 0; 0; 1; 1 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC) |
0.00; 0.00; 0.00; 0.00; 0.04; 0.04 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 AE Related to the Study Drug |
22.2; 27.8; 2.2; 9.9; 10.2; 8.7 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion |
30.9; 35.8; 13.3; 15.0; 15.8; 11.9 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion. |
28.5; 32.7; 13.3; 11.8; 12.2; 10.3 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion. |
28.0; 32.1; 13.3; 7.6; 7.7; 7.1 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion. |
1.0; 1.2; 0.0; 4.9; 5.1; 4.0 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT00546871). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.