A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects With Primary Immunodeficiency Diseases (PID)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 16
- 主要终点
- Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
研究概览
简要总结
In this study, Japanese participants with primary immunodeficiency diseases were treated with Immune Globulin Subcutaneous (Human), 20% solution, (IGSC, 20%). This study will be in 3 parts:
Part 1: Infusions with Immunoglobulin Intravenous (IGIV) every 3 or 4 weeks for 13 weeks.
Part 2: Participants will switch to weekly subcutaneous infusions with IGSC, 20% for 24 weeks.
Part 3: A subset will receive biweekly subcutaneous infusions with IGSC, 20% for 12 weeks.
The main aim of the study is to assess base levels of Immunoglobulin globulin G (IgG) levels in the blood of the participants after weekly and biweekly treatment with IGSC, 20% (in Parts 2 and 3 of the study). Their PID will be treated by their doctor according to their doctor's usual clinical practice.
详细描述
This study consists of 3 treatment parts (Epoch 1, 2, 3). The total evaluation period of the study will be 57 weeks in which screening period is for 2-8 weeks and Epoch 1 is from Week 8 to Week 21, Epoch 2 is from Week 21 to Week 45, Epoch 3 is from Week 45 to Week 57.
Each participant will receive IGIV treatment in Epoch 1 for a total of 13 weeks, then switch to weekly subcutaneous (SC) treatment with IGSC, 20% in Epoch 2 for a total of 24 weeks and will continue into Epoch 3 for a total of 12 weeks of biweekly SC treatment with IGSC, 20%. Drug dose in Epoch 2 and Epoch 3 will be adjusted so that it will be an equivalent weekly dose of the dose administered in Epoch 1 and twice the dose administrated in Epoch 2 respectively. Epoch 2 will contain two periods, period 1: dose adjustment period (first 12 weeks) and period 2: evaluation period (second 12 weeks).
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
- •Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
- •Participants must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement. The diagnosis must be confirmed by the medical director prior to treatment with IGIV.
- •Participant is 2 years or older at the time of screening.
- •Written informed consent is obtained from either the participants or the participants legally authorized representative prior to any study-related procedures and study product administration.
- •Participant has been receiving a consistent dose of IGIV over a period of at least 3 months prior to screening equivalent to approximately 200-600 mg/kg-body weight (BW) per 3- 4 week period, as according to the product package insert
- •Participant has a serum trough level of IgG >= 5 gram per liter (g/L) at screening.
- •Participant has not had a serious bacterial infection within the 3 months prior to screening.
- •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 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/
- •Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
- •Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal (ULN) for the testing laboratory
- •Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/milli cubic meter [mm^3]).
- •Participant has presence of renal function impairment defined by estimated glomerular filtration rate (eGFR) is <60 milliliter per minute/ 1.73 square meter (mL/min/1.73m^2).
- •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), unless the disease-free period prior to screening exceeds 5 years.
- •Participant is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
- •Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome).
- •Participant has anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site.
- •Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
- •Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L), known anti IgA antibodies, and a history of hypersensitivity.
- •Participant is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening.
- •Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
- •Participant has a bleeding disorder, or a platelet count less than 20,000/ microliter (mcL), or, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous therapy.
- •Participant has total protein > 9 gram per deciliter (g/dL) or myeloma, or macroglobulinemia (IgM) or paraproteinemia.
- •Women of childbearing potential meeting any one of the following criteria:
- •Participant presents with a positive pregnancy test.
- •Participant is breast feeding.
- •Participant intends to begin nursing during the course of the study.
- •Participant does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study.
- •Participant has participated in another clinical study and has been exposed to an IP or device within 30 days prior to study enrollment.
- •Participant is scheduled to participate in another non-observational (interventional) clinical study involving an IP or device during the course of the study.
- •Participant has severe dermatitis that would preclude adequate sites for safe product administration.
研究组 & 干预措施
Epoch 1: IGIV 200-600 mg/kg
Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks.
干预措施: Immune Globulin Intravenous (IGIV) (Biological)
Epoch 2: IGSC (20%) 50-200 mg/kg
Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1.
干预措施: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) (Biological)
Epoch 3: IGSC (20%) 100-400 mg/kg
Participants who entered to Epoch 3 from Epoch 1 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2.
干预措施: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) (Biological)
结局指标
主要结局
Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
时间窗: Epoch 2 (period 2): Up to 24 weeks
Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed.
Epoch 3: Total Serum Trough Levels of IgG Antibodies
时间窗: Epoch 3: Up to Week 12
Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed.
次要结局
- Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG(Epoch 2: Week 21)
- Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)(Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13))
- Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses(Epoch 2: Week 21)
- Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG(Epoch 2: Week 21)
- Epoch 2: Tmax for Total Serum Levels of IgG Subclasses(Epoch 2: Week 21)
- Epoch 2: Cmin for Total Serum Levels of IgG Subclasses(Epoch 2: Week 21)
- Epoch 1: Total Serum Trough Levels of IgG Antibodies(Epoch 1: Up to Week 13)
- Epoch 2: Cmax for Total Serum Levels of IgG Subclasses(Epoch 2: Week 21)
- Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG(Epoch 2: Week 21)
- Number of Days Participants Were on Antibiotics(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score(Baseline up to end of study (approximately 1.5 years))
- Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score(Baseline up to end of the study (approximately 1.5 years))
- Epoch 2: CL/F for Total Serum Levels of IgG Subclasses(Epoch 2: Week 21)
- Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG(Epoch 2: Week 21)
- Number of Days Participants Not Able to Attend School or Work to Perform Normal Daily Activities Due to Illness/Infection(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG(Epoch 2: Week 21)
- Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)(Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of study drug up to end of study (up to approximately 1.5 years))
- EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score(Baseline up to end of the study (approximately 1.5 years))
- Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score(Baseline up to end of the study (approximately 1.5 years))
- Annual Rate of All Infections Per Year(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Length of Hospital Stay(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Number of Acute Physician Visits Due to Illness/Infection(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Health Related Quality of Life: Treatment Preference(Up to approximately 1.5 years)
- Number of Participants With Tolerability Events Related to the Infusion of Study Drug(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Number of Participants Hospitalized Due to Illness or Infection(From first dose of study drug up to end of study (up to approximately 1.5 years))
- Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score(Baseline up to end of the study (approximately 1.5 years))