Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human) 10% (IGIV, 10%) Administered Intravenously or Subcutaneously in Subjects With Primary Immunodeficiency Diseases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 9
- 主要终点
- Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 24 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
时间窗: 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
Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)
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
时间窗: Throughout study (1 year and 9 months)
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.
时间窗: Throughout study (1 year and 9 months)
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 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
时间窗: Throughout study (1 year and 9 months)
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
时间窗: Throughout study (1 year and 9 months)
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
时间窗: Throughout study (1 year and 9 months)
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
时间窗: Throughout study (1 year and 9 months)
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
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
时间窗: Week 12 (IV) and week 32 or 33 (SC)
Expressed as (AUC\_SC/AUC\_IV) \* 100
次要结局
- Study Part 1 (IV): Maximum Plasma Concentration (C-max)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.)
- Study Part 1 (IV): Minimum Plasma Concentration (C-min)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.)
- Study Part 1 (IV): Weight-adjusted Clearance(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.)
- Study Part 1 (IV): Terminal Half-life(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.)
- Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 2 (SC): Minimum Plasma Concentration (C-min)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 2 (SC): Weight-adjusted Clearance(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 3B: Maximum Plasma Concentration (C-max)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 3B: Minimum Plasma Concentration (C-min)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs(During Infusion or Within 72 Hours of Completion of Infusions)
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)(Throughout entire study (1 year and 9 months))
- Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)(Throughout entire study (1 year and 9 months))
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages)(Throughout entire study (1 year and 9 months))
- Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages)(Throughout entire study (1 year and 9 months))
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)(Throughout entire study (1 year and 9 months))
- Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)(Throughout entire study (1 year and 9 months))
- Percentage of Infusions Associated With ≥1 AE Related to the Study Drug(Throughout the study period (1 year and 9 months))
- Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion(During Infusion or Within 72 Hours of Completion of Infusions)
- Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.(During Infusion or Within 72 Hours of Completion of Infusions)
- Study Part 3B: Area Under the Curve (AUC)(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Study Part 3B: Weight-adjusted Clearance(Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.)
- Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older(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)
- Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants(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)
- Trough Levels of Antibody to Hepatitis B in All Study Participants(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)
- Trough Levels of Antibody to Tetanus In All Study Participants(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)
- Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level(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)
- Annual Infection Rates During Treatment(Throughout the study, 1 year and 9 months)
- Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS)(Throughout the study, 1 year and 9 months)
- Rate of Temporally Associated AEs Per Infusion(During Infusion or Within 72 Hours of Completion of Infusions)
- AEs Deemed/Judged to be Related by the Investigator(Throughout the study period (1 year and 9 months))
- Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L)(Throughout the study period (1 year and 9 months))
- Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.(During Infusion or Within 72 Hours of Completion of Infusions)
- Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.(During Infusion or Within 72 Hours of Completion of Infusions)