Long-Term Tolerability and Safety of Immune Globulin Subcutaneous (IGSC) Solution Administered Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Primary Immunodeficiency Diseases
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 11
- 主要终点
- Annual Rate of All Infections
研究概览
简要总结
The original purpose of the study is to assess the long-term safety, tolerability, and practicability of the subcutaneous (SC) treatment with Immune Globulin Subcutaneous Solution (IGSC), 10% facilitated with recombinant human hyaluronidase (rHuPH20) in participants with Primary Immunodeficiency Diseases (PID) who have completed Baxter Clinical Study Protocol No. 160603.
Following a discussion with the FDA, all participants still active in the study stopped treatment with rHuPH20 to assure safety of the participants participating in the study and went into a safety follow-up.
During this safety follow-up period, participants underwent either intravenous (IV) or SC treatment with IGSC, 10%. The IV or SC administration route was at the discretion of the participant and the investigator.
详细描述
IGSC, 10% is the same product as IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% (IGIV, 10%) quoted in study 160603.
IGSC, 10% is abbreviated to IGI, 10% [IMMUNE GLOBULIN INFUSION (HUMAN), 10%]
In the US the product is licensed (trade name GAMMAGARD LIQUID) for the intravenous (IV) and SC replacement therapy of antibody deficiency in patients with PID.
In the EU this product is licensed (trade name KIOVIG)
IGSC, 10% with rHuPH20 established name is Innume Glubulin Infusion 10% (Human) with Recombinant Human Hyualuronidase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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 has completed or is about to complete Baxter Clinical Study Protocol No.
- •Participants who have discontinued rHuPH20 and reverted to intravenous or subcutaneous treatment due to an anti-rHuPH20 antibody also may enroll for long-term safety monitoring.
- •Participant/caretaker has reviewed, signed and dated informed consent
- •Participant is willing and able to comply with the requirements of the protocol
排除标准
- •Participant has a serious medical condition such that the participant's safety or medical care would be impacted by participation in Study 160902
- •Participant is scheduled to participate in another non-Baxter clinical study involving an investigational product or investigational device during the course of this study
- •If female of childbearing potential, participant is pregnant or has a negative pregnancy test and does not agree to employ adequate birth control measures for the duration of the study
结局指标
主要结局
Annual Rate of All Infections
时间窗: Throughout the efficacy period only (from 60 to 729 days)
Annualized rate of infections per participant as defined by MedDRA system organ class (SOC) "infections and infestations". The point estimate of the annual rate of all infections was provided during subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20). This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.
Trough Levels of IgG Maintained During the Study Period in Relation to Dose Frequency
时间窗: Throughout the efficacy period only (from 60 to 729 days)
Immunoglobulin (IgG) steady state trough levels were measured in relation to dose frequency by measuring in relation to treatment interval (2-, 3- or 4-week intervals). Initially participants were administered subcutaneous (SC) infusions of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20) \[or IV infusions of IGSC, 10% only\] at the treatment intervals and dose determined by epoch 2 of study 160603 (3- or 4-week intervals). After 3 treatment intervals (either 3- or 4- week intervals), participants changed to a 2-week treatment interval, if agreed with participant and investigator, with the dose adjusted to 1/2 of the 4-week dose or 2/3 of the 3-week dose, whichever was applicable. The rHuPH20 dose was adjusted relative to the new IGSC, 10% dose in order to achieve a dose ratio of 75 U/g IgG. This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.
Annual Rate of Serious Bacterial Infections
时间窗: Throughout the efficacy period only (from 60 to 729 days)
The point estimate of the annual rate of validated acute serious bacterial infections (VASBIs) per participant per year was provided during subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20). This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.
次要结局
- Percentage of Infusions Associated With One or More Moderate or Severe AEs (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of an Infusion(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- The Annual Rate of Serious Adverse Events (SAEs), Related and Not Related to Study Drugs(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for AEs(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Number of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20(Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months))
- Number of Participants With AEs Related to Anti-rHuPH20 Titers(Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months))
- Percentage of Participants With AEs Related to Anti-rHuPH20 Titers(Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months))
- Percentage of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20(Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months))
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (A-F).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (G-M).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (N-Z).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of AEs Per Participant (Including and Excluding Infections) Temporarily Associated With the Infusion(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of AEs Per Participant (Including and Excluding Infections) Determined by the Investigator to be Related to the Study Drug That Occur at Any Time During the Study ("Related")(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of AEs Per Infusion (Including and Excluding Infections) Determined by the Investigator to be Related to the Study Drug That Occur at Any Time During the Study ("Related")(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Rate of AEs Per Infusion (Including and Excluding Infections) Temporarily Associated With the Infusion(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)
- Percentage of Infusions Associated With One or More Local AEs (Including and Excluding Infections), at Any Time During the Study(Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer.)