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临床试验/NCT00814320
NCT00814320已完成3 期

Efficacy, Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human), 10% (GAMMAGARD LIQUID/KIOVIG) Administered Intravenously or Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Primary Immunodeficiency Diseases

Baxalta now part of Shire14 个研究点 分布在 2 个国家目标入组 89 人开始时间: 2008年12月18日最近更新:
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适应症

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
89
试验地点
14
主要终点
Validated Acute Serious Bacterial Infection (VASBI) Rate
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of the study is to develop a subcutaneous treatment option for participants with Primary Immunodeficiency Diseases (PID) that allows an administration of Immune Globulin Intravenous (Human), 10% at the same frequency as IV administration.

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
2 Years 至 —（Child, Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participant is 2 years or older at the time of screening
  • •Written informed consent obtained from either the participant or the participant's legally acceptable representative prior to any study-related procedures and study product administration
  • •Participant has been diagnosed with a PID disorder requiring antibody replacement as defined by WHO criteria
  • •Participant has completed or is about to complete Baxter Clinical Study Protocol No. 160601 or has been receiving a regular IGIV-treatment at mean intervals of 21 ± 3 days or 28 ± 3 days, or SC at mean intervals of 5 to 16 days, over a period of at least 3 months prior to enrollment at a minimum dose of 300 mg/kg BW/4 weeks
  • •Participant has a serum trough level of IgG > 4.5 g/L at the last documented determination
  • •If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study
  • •Participant is willing and able to comply with the requirements of the protocol

排除标准

  • •Participant has a known history of or is positive at enrollment or screening for one or more of the following: Hepatitis B surface antigen (HbsAg), polymerase chain reaction (PCR) for Hepatitis C Virus (HCV), PCR for Human immunodeficiency virus (HIV) Type 1/2
  • •Participant has levels of alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
  • •Participant has persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
  • •Participant has creatinine clearance (CLcr) values, calculated according to the formula below, which are < 60% of normal for age and gender for males: CLcr = [(140 - Age(years)) * (body weight (kg))] / [72 * (serum creatinine (mg/dL))] for females: CLcr = [(140 - Age(years)) * (body weight(kg)) * 0.85] / [72 * (serum creatinine (mg/dL))]
  • •Participant has been diagnosed with, or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within the last 12 months prior to enrollment; participants treated with immunosuppressive chemotherapeutic agents during this period are excluded
  • •Participant has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months
  • •Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome)
  • •Participant has anemia that would preclude phlebotomy for laboratory studies
  • •Participant has 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 enrollment
  • •Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin, and/or ISG infusions
  • •Participant has immunoglobulin A (IgA) deficiency and known anti IgA antibodies
  • •Participant is on preventative (prophylactic) antibiotics and cannot stop antibiotics at the time of enrollment
  • •Participant has active infection who started on antibiotic therapy for the treatment of infection within 7 days prior to screening
  • •Participant has a bleeding disorder or is on anti-coagulation therapy that results in a platelet count less than 20,000/μL or International Normalized Ration (INR) > 2X control, or who, in the opinion of the investigator would be at significant risk of increased bleeding or bruising as a result of SC therapy
  • •Participant has total protein > 9 g/dL and participants with myeloma, macroglobulinemia (IgM) and paraproteinemia
  • •Participant has a known allergy to hyaluronidase
  • •If female, participant is pregnant or lactating at the time of study enrollment
  • •Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study; exception: Baxter Study No. 160601
  • •Severe dermatitis that would preclude adequate sites for safe product administration

结局指标

主要结局

Validated Acute Serious Bacterial Infection (VASBI) Rate

时间窗: Throughout the study period (17 months)

Serious acute bacterial infections include bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess that are caused by a recognized bacterial pathogen. VASBI rate is the mean number of VASBIs per participant per year, recorded for SC Administration of IGIV, 10%, with rHuPH20 after ramp-up, only. The mean number of VASBIs per participant per year and the 99% upper confidence limit for the acute serious bacterial infection rate were calculated using a Poisson model to account for the length of the observation periods per participant.

次要结局

  • Bioavailability (AUC) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants ≥12 Years(PK AUC evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion)
  • Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants Aged 2 to < 12 Years(IgG trough levels measured at baseline and on day of each 3- or 4-week infusion for infusion for IV and SC (except during ramp-up for SC) and at end of study visit)
  • Bioavailability (AUC) of IgG After SC Administration of IGIV, 10%, Given With and Without rHuPH20(PK: 160603 (IV: before infusion (inf.) #4 [3-week treatment interval] or inf. #3 [4-week treatment interval];SC: before last SC inf.) 1 hour pre-inf. ≤28 days (+/-2 days) post-inf.; 160601- 1 hour pre-inf. (before inf. #8) ≤7 days (+/-1 day) post-inf.)
  • Annual Rate of All Infections Per Participant(Throughout the study period (17 months))
  • Trough Levels of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20(IgG trough levels measured at baseline and on day of each 3- or 4-week infusion for IV and SC (except during ramp up for SC) and at end of study visit.)
  • Trough Levels of IgG Subclasses After Administration of IGIV, 10% Given Via IV or SC With rHuPH20(IgG subclasses (1-4) trough levels measured at baseline and on day of each 3- or 4-week infusion for infusion for IV and SC (except during ramp up for SC) and at end of study visit)
  • Antibody Levels to Tetanus (Clostridium Tetani Toxoid)(IV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit)
  • IgG Terminal Half Life (T1/2) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Time to Maximum IgG Concentration (T-max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Tetanus Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Tetanus Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • H. Influenzae Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Antibody Levels to Haemophilus Influenzae(IV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit)
  • IgG Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion)
  • Antibody Levels to Measles(IV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit)
  • Antibody Levels to Hepatitis B(IV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit)
  • IgG Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • IgG Clearance (CL) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • IgG Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Tetanus Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Tetanus Antibody Clearance (CL) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Tetanus Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Time to Maximum Tetanus Antibody Concentration (T-max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • H. Influenzae Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • H. Influenzae Antibody Clearance (CL) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • H. Influenzae Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for Adverse Events (AEs)(Throughout the study period (17 months))
  • Rate of Temporally Associated AEs Per Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of Participants Reporting ≥1 Temporally Associated AEs(During infusion or within 72 hours of completion of infusion)
  • Percentage of Infusions Resulting in ≥1 Temporally Associated AEs(During infusion or within 72 hours of completion of infusion)
  • H. Influenzae Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Time to Maximum H. Influenzae Antibody Concentration (T-max) for Participants Aged 12 Years and Older(PK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.)
  • Rate of Days Off School or Work(Monthly, for up to 17 months)
  • Rate of Days on Antibiotics(Monthly, for up to 17 months)
  • Rate of Acute Physician Visits(Monthly, for up to 17 months)
  • Rate of Days in Hospital(Monthly, for up to 17 months)
  • Percentage of Participants for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for Adverse Events (AEs)(Throughout the study period (17 months))
  • Percentage of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs(During infusion or within 72 hours of completion of infusion)
  • Percentage of Infusions Resulting in ≥1 Temporally Associated Moderate or Severe AEs Within 72 Hours of Completion of Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of SC Doses of IGIV, 10% and rHuPH20 Tolerated at 1 Infusion Site(During infusion or within 60 minutes of completion of the infusion)
  • Percentage of Infusions Associated With ≥1 Systemic AE During Infusion or Within 72 Hours of Completion of Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of Participants With ≥1 Systemic AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of Infusions Associated With ≥1 Local AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of Infusions Associated With ≥1 Local AE At Any Time During the Study(At any time during the study)
  • Percentage of Participants With ≥1 Local AE During Infusion or Within 72 Hours of Completion of Infusion(During infusion or within 72 hours of completion of infusion)
  • Percentage of Participants With ≥1 Local AE At Any Time During the Study(During infusion or within 72 hours of completion of infusion)
  • Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Participant(Throughout the study period (17 months))
  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (A-F)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (G-M)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (A-F)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (G-M)(Throughout the study period (17 months))
  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (G-M)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (N-Z)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (N-Z)(Throughout the study period (17 months))
  • Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (A-F)(Throughout the study period (17 months))
  • Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Infusion(Throughout the study period (17 months))
  • Frequency of Dose Corrections (If IgG Trough Levels <4.5 g/L) for Each Study Epoch (IV and SC/rHuPH20 Treatment)(Throughout the study period (17 months))
  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (N-Z)(Throughout the study period (17 months))
  • Percentage of Infusions Associated With ≥1 AE Related to Either or Both Study Drugs(Throughout the study period (17 months))
  • Percentage of Infusions Tolerated With IV and SC Administration at Dose Used in Study Epoch 2 (SC/rHuPH20 Treatment)(Throughout the study period (17 months))
  • Median Rate of AEs Temporally Associated or Related to Study Drug Per Infusion(Throughout the study period (17 months))
  • Number of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)(Throughout the study period (17 months))
  • Percentage of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)(Throughout the study period (17 months))
  • Number of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further Analysis(Throughout the study period (17 months))
  • Percentage of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further Analysis(Throughout the study period (17 months))

研究者

发起方
Baxalta now part of Shire
申办方类型
Industry
责任方
Sponsor

研究点 (14)

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